Early Uptake of Breast Magnetic Resonance Imaging

纹理分析在肿瘤影像组学中的临床应用陈国钰; 沈桂权; 高波【期刊名称】《《贵州医药》》【年(卷),期】2019(043)007【总页数】3页(P1037-1039)【关键词】纹理分析; 影像组学; 肿瘤; 应用【作者】陈国钰; 沈桂权; 高波【作者单位】贵州医科大学附属医院影像科贵州贵阳550004; 烟台毓璜顶医院影像科山东烟台264000【正文语种】中文【中图分类】R445为精确反映整个肿瘤内部的生物学信息，人们使用计算机技术挖掘医学图像中的特征空间数据——影像组学已成为影像学研究的最新目标[1]。

影像组学把全部肿瘤作为研究客体，能全面评估肿瘤内部的异质性等生理情况，取得临床及传统影像学无法获得的信息。

纹理分析(texture analysis，TA)是影像组学中的一部分，是医学图像中近年才发展起来的评价肿瘤异质性的新工具。

1 TA的概念纹理是图像中非常基本且有用的信息特征，也是图像处理分析的重要参考参数。

应用不同的提取方法得到不同的纹理特征，反映不同的生理或病理信息。

对图像进行纹理分析能得到更全面的信息，是行之有效且安全无创的。

2 TA的方法总的来说，纹理分析的方法有三种：统计分析法[2]、模型分析法[3]和变换分析法[4]。

2.1 统计分析法这是研究及使用最多的纹理分析方法，也是最先研究的一种方法，它不像直方图法不能反映空间位置信息。

根据特征计算时使用1个像素、2个像素或者3个及以上像素，把其分为一阶统计量、二阶统计量和高阶统计量。

2.2 模型分析法模型法把图像中的各个像素内部之间看作有着某种函数关系，在整体上估计出全部像素的空间位置关系。

模型法需要先了解图像内部基元的排列结构情况，以便选择合适的模型，再评估模型的相关系数，最后进行纹理特征的提取。

模型分析法是使用复杂数学模型来描述图像中的纹理，它的计算相当复杂，对简单纹理适用，但对于结构复杂的纹理要使用多种模型进行分块评估。

2.3 变换分析法它是在不同的空间分析图像中的纹理特性，比如不同的频率空间或尺度空间。

2000;41:1973-1979.J Nucl Med.Houlihan, Rhonda M. Jenkins and Stephen B. Haber Iraj Khalkhali, Javier Villanueva-Meyer, Steven L. Edell, James L. Connolly, Stuart J. Schnitt, Janet K. Baum, Mary J.Tc-Sestamibi Breast Imaging: Multicenter Trial Results99m Diagnostic Accuracy of/content/41/12/1973This article and updated information are available at:/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at:/site/misc/permission.xhtml Information about reproducing figures, tables, or other portions of this article can be found online at: (Print ISSN: 0161-5505, Online ISSN: 2159-662X)1850 Samuel Morse Drive, Reston, VA 20190.SNMMI | Society of Nuclear Medicine and Molecular Imaging is published monthly.The Journal of Nuclear Medicine© Copyright 2000 SNMMI; all rights reserved.Diagnostic Accuracy of99m Tc-Sestamibi Breast Imaging:Multicenter Trial ResultsIraj Khalkhali,Javier Villanueva-Meyer,Steven L.Edell,James L.Connolly,Stuart J.Schnitt,Janet K.Baum,Mary J.Houlihan,Rhonda M.Jenkins,and Stephen B.HaberDepartment of Radiology,Harbor UCLA Medical Center,Torrance,California;Department of Radiology,The University of Texas Medical Branch at Galveston,Galveston,Texas;Women’s Imaging Center of Delaware,Newark,Delaware;Departments of Pathology, Radiology,and Surgery,Beth Israel Deaconess Medical Center,Boston,Massachusetts;and DuPont Pharmaceuticals Company, Wilmington,Delaware,and North Billerica,MassachusettsAlthough mammography is well established as afirst-line tool for breast cancer screening and detection,efforts to develop comple-mentary procedures continue.Observation of99m Tc-sestamibi tumor uptake provided the impetus for its evaluation as an adjunctive technique.This trial’s objectives were to determine in a multicenter trial the diagnostic accuracy of99m Tc-sestamibi in women with suspected breast cancer and to investigate factors influencing diagnostic accuracy.Methods:Our multicenter trial enrolled673women(387with nonpalpable abnormalities;286 with palpable abnormalities)scheduled for excisional biopsy or mastectomy.Blinded and unblinded interpretations of scinti-graphic images were compared with core laboratory established histopathologic diagnoses to define the diagnostic accuracy of 99m Tc-sestamibi breast imaging.Results:Blinded readers’diag-nostic accuracy was78%–81%.Inter-reader agreement was excellent,ranging from95%to100%(␬ϭ0.82–0.99).Overall institutional sensitivity and specificity for99m Tc-sestamibi breast imaging were75.4%and82.7%,respectively.In this population with a40.1%disease prevalence,the positive predictive value was74.5%and the negative predictive value was83.4%.The negative predictive value was94%in patients with a40%or lower mammographic likelihood of breast cancer.Sensitivity was higher for palpable abnormalities;specificity was higher for nonpalpable abnormalities.Sensitivity was decreased for tumors Ͻ1cm in largest dimension but appeared not to be affected by patient’s age.Conclusion:As an adjunct to current procedures, 99m Tc-sestamibi breast imaging may contribute to patient manage-ment decisions in selected populations,including women with dense breasts,mammographically indeterminate lesionsϾ1cm, and palpable abnormalities.Key Words:scintimammography;99m Tc-sestamibi;breast can-cer;breastJ Nucl Med2000;41:1973–1979B reast cancer is the most common malignancy of Ameri-can women after skin cancer and the leading cause of nonpreventable cancer death(1).Breast self examination, clinical breast examination,and screening mammography are the recommended procedures for early breast cancer detection.Screening mammography has been shown to reduce breast cancer mortality in women40–69y old(2,3), although the benefit reported in women40–49y old(3)is somewhat less than that reported in the older population(2). Still greater reduction in mortality is sought,and there is a clear need to extend the full benefit to women of all ages. Thus,intensive efforts in early diagnosis have focused on improvements in patient outcomes by developing proce-dures that improve the sensitivity and positive predictive value of the procedures used to evaluate patients with suspected breast cancer.99m Tc-sestamibi is a radiopharmaceutical that was origi-nally developed as a myocardial perfusion imaging agent. However,results from in vitro(4–6)and in vivo(7–10) preclinical studies have suggested that it may have potential as a tumor imaging agent.Several investigators have reported results of breast imaging with99m Tc-sestamibi that have generally supported this potential(11–20).The objec-tives of our study were to extend these earlier results by determining in a multicenter trial the diagnostic accuracy of 99m Tc-sestamibi in women with suspected breast cancer and to investigate factors influencing diagnostic accuracy. MATERIALS AND METHODSSubjectsSix hundred seventy-three women were enrolled at42institu-tions in the United States and Canada.Enrollment occurred from April1994through May1995.For enrollment in the trial,the subjects were to be already scheduled for an excisional biopsy(or mastectomy)on the basis of the presence of a nonpalpable mammographically detected breast abnormality or a palpable breast abnormality;387women with nonpalpable abnormalities and286women with palpable abnormalities were enrolled.As in clinical practice,women with palpable abnormalities did not necessarily have mammographic abnormalities.Because prelimi-nary pilot work had suggested that trauma could lead to false-positive99m Tc-sestamibi images,subjects could not have under-gonefine-needle aspiration or core needle biopsy within1wk before the99m Tc-sestamibi imaging study.To be evaluable,subjects had to have an abnormality identified by palpation or mammogra-phy(or both),99m Tc-sestamibi scintigraphy,and excisional biopsyReceived Nov.29,1999;revision accepted May16,2000.For correspondence or reprints contact:Stephen B.Haber,PhD,DuPontPharmaceuticals Company,331Treble Cove Rd.,500-2,North Billerica,MA01862.99M T C-S ESTAMIBI B REAST I MAGING•Khalkhali et al.1973(or mastectomy)in that sequence;563women met evaluability criteria(315with nonpalpable abnormalities and248with palpable abnormalities).The investigational protocol was approved by the institutional review board at each participating center,and each subject provided written informed consent.MammographyMammography was performed using standard craniocaudal and mediolateral oblique views with additional views obtained as clinically indicated.Each participating site in the United States was accredited by the American College of Radiology Mammography Accreditation Program.The Canadian site had full accreditation in medical imaging by the Diagnostic Accreditation Program in British Columbia.Additionally,phantom images and representa-tive mammograms from each site were evaluated by the mammog-raphy core center.Deficiencies noted by the core center were corrected before enrolling patients.Collection of mammography results was based on the American College of Radiology Breast Imaging Reporting and Data System(21).Although it is not a common practice,for this trial the mammographer at each site assigned a mammographic probability of malignancy to each lesion (palpable or nonpalpable)that was to be biopsied.The parenchy-mal patterns‘‘heterogeneously dense’’and‘‘extremely dense’’were defined to represent dense breasts,whereas‘‘almost entirely fat’’and‘‘numerous vague densities’’were defined to represent fatty breasts.ScintigraphyPlanar imaging with high-resolution collimation was performed using the gamma cameras available in the investigators’depart-ments.Subjects received a740-to1110-MBq(20–30mCi)bolus intravenous injection of99m Tc-sestamibi in the arm contralateral to the suspicious breast abnormality;subjects with bilateral abnormali-ties were injected in a dorsalis pedis vein.Five minutes after injection,a10-min lateral view of the breast scheduled for biopsy was obtained with the subject positioned prone on an imaging table overlay(Bodfish Research and Design,Inc.,Bodfish,CA)so that the breast being imaged was pendent(11).The subject was then repositioned to obtain a lateral view of the contralateral breast followed by a supine anterior teral views were repeated1h after injection.Scintigraphic images were read at the sites by the investigators (institutional results).Because most investigators in the trial had minimal experience interpreting99m Tc-sestamibi breast images,a set of18images,scored on a5-point scale(0ϭnormal;1ϭequivocal;2ϭfocal uptake,low intensity;3ϭfocal uptake, medium intensity;and4ϭfocal uptake,high intensity)but with-out histopathologic correlation,was provided for image scoring training.For the calculation of diagnostic statistics,scores of2–4were considered positive,scores of0were considered negative,and scores of1were considered uninterpretable and were not analyzed. Overall,institutional readers scored6.4%of biopsied scintigraphic abnormalities as1.In addition to the image interpretation by the investigators,two groups of three independent nuclear medicine physicians who had no knowledge of the subjects’clinical history, institutional scintigraphic results,or other test results(blinded readers)interpreted the images.Thus,the blinded readers were not told whether they were reading images from subjects with nonpal-pable abnormalities or with palpable abnormalities.One group of blinded readers read the images from subjects with nonpalpable abnormalities,and the other group read the images from subjects with palpable abnormalities.For the blinded reading,digital data were converted to a common image display format,and images were randomized and read from the computer display.Lesion CorrelationBecause breast tissue is highly mobile and because mammo-graphic and scintigraphic imaging used different views and tech-niques(compressed versus noncompressed),it was necessary to review the scintigraphicfindings to establish lesion correlation. Thus,a radiologist not associated with the trial reviewed the scintigraphic images and mammograms in conjunction with the blinded readers’image interpretations and the investigational sites’mammographic data reporting to determine whether the scinti-graphic abnormality corresponded to the same tissue as the mammographicfinding.Similarly,a breast surgeon not associated with the trial reviewed the scintigraphic images,blinded readers’image interpretation,and the investigational sites’physicalfinding reporting to determine whether the scintigraphic abnormality corresponded to the same tissue as the palpable abnormality.All calculations of diagnostic statistics were based on histopathologi-cally determined malignancy or benignity of biopsied tissue. Because a scintigraphic abnormality that did not correspond to a mammographic abnormality or physicalfinding was not biopsied, such abnormalities could not be assigned as malignant or benign and thus were excluded from analysis.Characterization of these scintigraphic abnormalities as either false-positive or true-positive findings is the objective of a follow-up study.Biopsy and HistopathologyBiopsy decisions were based on clinical presentation indepen-dent of scintigraphicfindings.After needle localization,excision of nonpalpable mammographically detected abnormalities was con-firmed by specimen radiography.The institutional histopatholo-gists determined tumor size from excised tissue specimens.Histo-pathologic diagnosis by the core laboratory was based solely on excisional biopsy or mastectomy specimens.Evaluation was performed on original slides or recuts of the tissue blocks if originals were unavailable.Ductal carcinoma in situ(DCIS), infiltrating ductal carcinoma,and infiltrating lobular carcinoma were classified as malignant.Cases of lobular carcinoma in situ were classified as nonmalignant.Statistical AnalysisThe primary analysis in evaluating99m Tc-sestamibi for detecting the presence of malignancy compared the blinded reader’s image interpretation with the histopathologic diagnosis.Sensitivity,speci-ficity,positive and negative predictive values,and accuracy were parisons between two groups were performed using a two-sample test of proportions.Group differences were considered significant at PϽ0.05.Inter-reader agreement was assessed using the␬statistic.␬Ͻ0.40indicates poor agreement, whereas␬ϭ0.40–0.75and␬Ͼ0.75indicate fair-to-good and strong agreement,respectively(22).To further investigate factors influencing diagnostic results,a multivariable regression analysis was performed.Variables entered into the model included patient age dichotomized asՅ50orϾ50y, mammographers’likelihood of malignancy,mammographicfind-ing categorized as mass or calcification,lesion palpability,and tumor size dichotomized asϽ1orՆ1cm.1974T HE J OURNAL OF N UCLEAR M EDICINE•V ol.41•No.12•December2000RESULTSThe prevalence of malignancy was40.1%overall:48.4%for palpable abnormalities and32.9%for nonpalpableabnormalities.The mean age of the evaluable subjects was52.2y(range,23–85y);31.6%were premenopausal and49.5%had dense breasts.Women with nonpalpable abnor-malities were older,less likely to be premenopausal,and lesslikely to have dense breasts than were women with palpableabnormalities(Table1).The overall institutional sensitivity and specificity for99m Tc-sestamibi breast imaging were75.4%and82.7%,respectively.Sensitivity was higher and specificity waslower for palpable abnormalities compared with nonpal-pable abnormalities(PϽ0.05).Specificity was higher andsensitivity was lower for the blinded readers compared withthe institutional results.These differences in sensitivity andspecificity tended to be balanced,because the diagnosticaccuracy for the blinded readers and institutional readers forpalpable and nonpalpable abnormalities were similar,rang-ing from78%to81%(Figs.1and2).AgeThe group of women who wereՅ50y old with nonpal-pable abnormalities had a disease prevalence of21.2%,whereas the group of younger women with palpable abnor-malities had a prevalence of malignancy of34.0%.Theoverall diagnostic sensitivity for99m Tc-sestamibi breastimaging was comparable in womenՅ50y old and women Ն50y old(75.3%and75.5%,respectively;Pϭnot significant).When the results were considered separately forwomen with palpable abnormalities and for women withnonpalpable abnormalities,there was a trend for highersensitivity in older women,although these differences werenot statistically significant(Table2).Imaging specificitywas higher in the older population,although this differencewas not statistically significant for institutional results forwomen with palpable abnormalities.Tumor SizeDiagnostic sensitivity of any imaging procedure is af-fected by limitations inherent in the procedure(e.g.,scintil-lation camera resolution).Consequently,we assessed sensi-tivity for the detection of nonpalpable abnormalities as afunction of the largest tumor dimension measured on the excised specimen.Institutional sensitivity was significantlyhigher for tumorsՆ1cm than for tumorsϽ1cm(74.2%and48.2%,respectively;PϽ0.05).Similar results were ob-served for the blinded readers.Likelihood of MalignancyThe prevalence of histopathologically determined diseasewas well tracked by the mammographers’estimate of alesion’s likelihood of being malignant(rϭ0.98;PϽ0.005).The institutional sensitivity and specificity of99m Tc-sestamibi imaging were similar in women with all likeli-hoods of disease,64%–82%and73%–87%,respectively(Table3).Consequently,in women withՅ40%mammo-graphic likelihood of malignancy,the negative predictivevalue for99m Tc-sestamibi imaging was94%.Invasive Cancer Versus DCISAlthough our primary analysis classified DCIS as malig-nant,cognizant of the controversy over whether all DCISprogresses to invasive cancer,we also analyzed the sensitiv-ity for invasive cancer and for DCIS separately.Overallinstitutional sensitivity was82.0%for invasive cancer and45.9%for DCIS(PϽ0.001).For women with palpableabnormalities,sensitivity was90.5%for invasive cancer and57.1%for DCIS(Pϭ0.002).For women with nonpalpableabnormalities,sensitivity was69.2%for invasive cancer and39.1%for DCIS(Pϭ0.02).Time of ImagingWe were interested in evaluating the impact of time ofimaging after99m Tc-sestamibi injection on diagnostic accu-racy because99m Tc-sestamibi tumor efflux could lead todecreased diagnostic sensitivity for delayed imaging.Over-all institutional results showed a modest decrease in sensitiv-ity for delayed imaging and a corresponding increase inspecificity.However,diagnostic accuracy(Table4)and areaunder the receiver operating characteristic curve were com-parable for early and delayed imaging.Consequently,toensure highest sensitivity for the identification of malignantabnormalities,we recommend early scintigraphic imagingonly.Inter-Reader AgreementReproducibility for the detection of malignancy amongthe blinded readers was very high.Inter-reader agreementamong the three blinded readers who read scintigraphicimages from subjects with palpable abnormalities rangedfrom96%to100%(␬ϭ0.93–0.99).Inter-reader agreementfor evaluation of nonpalpable abnormalities ranged from95%to96%(␬ϭ0.82–0.89).Multivariable Regression AnalysisThe only independent predictors of a true-positive99m Tc-sestamibi image in the multivariable regression analysiswere lesion palpability and tumor size(global␹2ϭ37.7). The analysis was also conducted excluding tumor size,aswould occur for abnormalities detected solely as microcalci-TABLE1 Subject DemographicsParameterAllsubjectsAbnormalitiesPalpable NonpalpableAge*(y)52.2Ϯ12.649.4Ϯ13.254.3Ϯ11.7Յ50y old(%)4957.342.5Premenopausal(%)31.641.124.1Dense breasts(%)49.557.643.4*MeanϮSD.99M T C-S ESTAMIBI B REAST I MAGING•Khalkhali et al.1975fications.Lesion palpability became the only predictive variable in that model.DISCUSSIONApproximately 25million mammographic examinations are performed annually in the United States for the screening and diagnosis of breast cancer.Despite widespread clinical acceptance and extensive refinement,5%–15%of breast cancers are not visualized by this procedure.Some breast parenchymal patterns may compromise definitive mammo-graphic interpretation and a large percentage of mammo-graphically missed carcinomas have been ascribed to prob-lems associated with imaging the dense breast (23).Highly nodular breasts,breasts with diffuse patterns of indistinct microcalcifications,and postsurgical parenchymal scarring and distortion of normal breast tissue associated with implants or radiation therapy pose additional challenges to the radiologist.Improvements in mammography techniques and proce-dures can certainly overcome some of these interpretivechallenges.However,an adjunctive technique such as 99m Tc-sestamibi breast imaging,which relies on characteris-tics of tumor growth,has promise as a tool to assist in resolving difficult-to-interpret mammograms.Earlier studies of 99m Tc-sestamibi breast imaging reported diagnostic sensitivities ranging from 83%to 96%and specificities ranging from 83%to 94%in populations with disease prevalence ranging from 29%to 84%(11–20).Although some of these reports evaluated 99m Tc-sestamibi breast imaging of both palpable and nonpalpable abnormali-ties,any attempt to estimate diagnostic sensitivity from these 10earlier studies would be based on results from only 13nonpalpable cancers.Thus,although these single center studies were limited by their focus on palpable abnormalities and their referral bias as evidenced by the high prevalence of disease,they did suggest the value of more systematically studying the diagnostic performance of 99m Tc-sestamibi breast imaging.More recently,reports have appeared from multicenter studies conducted in Europe.The European multicenter trial reported an overall blinded sensitivityofFIGURE 1.Diagnostic statistics for 99m Tc-sestamibi breast imaging in patients with palpable abnormalities.PPV ϭpositive pre-dictive value;NPV ϭnegative predictivevalue.FIGURE 2.Diagnostic statistics for 99m Tc-sestamibi breast imaging in patients with nonpalpable abnormalities.PPV ϭpositive predictive value;NPV ϭnegative predictive value.1976T HE J OURNALOFN UCLEAR M EDICINE •V ol.41•No.12•December 200071%in a population with65%disease prevalence,a sensitivity for palpable malignancy of83%,and a sensitivity for nonpalpable malignancy of30%(24).The Spanish multicenter study reported an overall blinded sensitivity of 90%in a population with59%disease prevalence,a sensitivity for palpable malignancy of94%,and a sensitivity for nonpalpable malignancy of75%(25).Similar to many of the single center reports,a high prevalence of disease represented a limitation to these studies.Additionally,the results for nonpalpable abnormalities are difficult to evaluate because only38nonpalpable malignancies were included in the European trial and,although126nonpalpable lesions were represented in the Spanish study,the number of nonpalpable malignancies is not reported.We examined the diagnostic accuracy of99m Tc-sestamibi breast imaging in women suspected of having breast cancer and scheduled for excisional biopsy or mastectomy.Diagnos-tic accuracy was also evaluated as a function of patient age, tumor size,and mammographers’estimate of likelihood of malignancy.The overall institutional sensitivity and specific-ity were75.4%and82.7%with a79.8%diagnostic accu-racy.In this population with a40.1%disease prevalence,theTABLE2Diagnostic Performance of99m Tc-Sestamibi Breast Imaging as Function of Patients’AgeParameterSensitivity(%)Specificity(%)PPV(%)NPV(%)Accuracy(%)Յ50y oldϾ50y oldՅ50y oldϾ50y oldՅ50y oldϾ50y oldՅ50y oldϾ50y oldՅ50y oldϾ50y oldOverall75.375.578.788.358.187.389.177.177.881.7 (61/81)(117/155)(163/207)(128/145)(61/105)(117/134)(163/183)(128/166)(224/288)(245/300) Palpable abnormalitiesInstitutional84.987.575.776.964.388.690.775.078.884.0 (45/53)(70/80)(78/103)(30/39)(45/70)(70/79)(78/86)(30/40)(103/156)(100/119) Reader170.879.277.588.263.093.483.166.775.282.1 (34/48)(57/72)(69/89)(30/34)(34/54)(57/61)(69/83)(30/45)(103/137)(87/106) Reader272.378.781.991.469.495.284.066.778.582.7 (34/47)(59/75)(68/83)(32/35)(34/49)(59/62)(68/81)(32/48)(102/130)(91/110) Reader371.477.983.889.568.693.885.666.779.781.7 (35/49)(60/77)(83/99)(34/38)(35/51)(60/64)(83/97)(34/51)(118/148)(94/115) Nonpalpable abnormalitiesInstitutional57.162.781.792.545.785.587.677.876.580.1 (16/28)(47/75)(85/104)(98/106)(16/35)(47/55)(85/97)(98/126)(101/132)(145/181) Reader450.052.888.898.153.895.087.275.780.780.0 (14/28)(38/72)(95/107)(106/108)(14/26)(38/40)(95/109)(106/140)(109/135)(144/180) Reader533.345.594.299.157.196.885.874.682.778.6 (8/24)(30/76)(97/103)(106/107)(8/14)(30/31)(97/113)(106/142)(105/127)(136/173) Reader644.856.687.493.950.086.084.976.478.078.9 (13/29)(43/76)(90/103)(107/114)(13/26)(43/50)(90/106)(107/140)(103/132)(150/190) PPVϭpositive predictive value;NPVϭnegative predictive value.TABLE3Diagnostic Performance of99m Tc-Sestamibi Breast Imaging as Function of Mammographic Likelihood of Breast CancerParameterMammographic likelihood of breast cancer0%–20%Ͼ20%–40%Ͼ40%–60%Ͼ60%–80%Ͼ80%–100%Sensitivity(%)68.082.463.665.081.1(17/25)(14/17)(14/22)(26/40)(99/122) Specificity(%)82.879.086.880.072.7(135/163)(49/62)(33/38)(12/15)(8/11) PPV(%)37.851.973.789.797.1(17/45)(14/27)(14/19)(26/29)(99/102) NPV(%)94.494.280.546.225.8(135/143)(49/52)(33/41)(12/26)(8/31) Accuracy(%)80.979.778.369.180.5(152/188)(63/79)(47/60)(38/55)(107/133)PPVϭpositive predictive value;NPVϭnegative predictive value.99M T C-S ESTAMIBI B REAST I MAGING•Khalkhali et al.1977positive predictive value was 74.5%and the negative predictive value was 83.4%.The sensitivity was lowest for nonpalpable tumors Ͻ1cm in their largest dimension.Screening mammography shows decreased sensitivity for invasive cancer in younger women compared with that of older women.Initially attributed to a higher prevalence of radiographically dense breasts in younger women,recent studies suggest that more rapid tumor growth and the greater prevalence of interval cancer in younger women may be the main cause of lower sensitivity (26,27).Multivariable regression analysis in this study showed that patient age was not predictive of a true-positive 99m Tc-sestamibi image.Additionally,previous reports have shown that the sensitiv-ity of 99m Tc-sestamibi breast imaging is comparable in patients with dense and fatty breasts (28,29).This suggests an adjunctive usefulness for 99m Tc-sestamibi breast imagingin younger patients,particularly in those with radiographi-cally dense breasts.We also compared the performance of mammography and 99m Tc-sestamibi scintimammography in the same popula-tion.The institutional 99m Tc-sestamibi scintimammography sensitivity and negative predictive value for patients with palpable abnormalities were comparable with mammogra-phy;however,the specificity and positive predictive value were higher (Fig.3).Evaluation of diagnostic imaging procedures often fo-cuses on the global presence of disease (e.g.,in a breast)without consideration of whether the specific imaged abnor-mality represents disease.Thus,although other reports have been limited by their lack of attention to this issue,one limitation of our study is the possibility of errors in the correlation of the location of scintigraphic abnormalities with the exact location of the palpable or mammographic abnormalities and with the excised tissue.The lesion correla-tion process also served to identify scintigraphic abnormali-ties that did not correspond to mammographic or palpable abnormalities,which could hence represent false-positive findings were biopsy information available on such abnor-malities.Preliminary studies of a scintigraphic needle local-ization technique (30)have shown the presence of malig-nancy in two of three patients with such scintigraphic abnormalities.Further development of this localization technique is essential to facilitate trials to better address issues of lesion correlation and the significance of scinti-graphic abnormalities that correspond to neither palpable nor mammographic abnormalities.Finally,our study is limited by subject enrollment criteria.Because each subject enrolled in this study was alreadyTABLE 4Diagnostic Performance by Imaging TimeParameter Early Delayed Sensitivity (%)75.471.1(178/236)(162/228)Specificity (%)82.787.1(291/352)(303/348)PPV (%)74.578.3(178/239)(162/207)NPV (%)83.482.1(291/349)(303/369)Accuracy (%)79.880.7(469/588)(465/576)PPV ϭpositive predictive value;NPV ϭnegative predictivevalue.FIGURE 3.Diagnostic statistics for 99m Tc-sestamibi breast imaging and for mam-mography in patients with palpable abnor-malities.PPV ϭpositive predictive value;NPV ϭnegative predictive value.1978T HE J OURNALOFN UCLEAR M EDICINE •V ol.41•No.12•December 2000scheduled for biopsy,our results should not be generalized to a screening population.However,the high negative predictive value in subjects with a low-to-intermediate likelihood of malignancy(Table3)does suggest an adjunc-tive value for99m Tc-sestamibi breast imaging. CONCLUSIONAs an adjunct to current diagnostic procedures,99m Tc-sestamibi breast imaging may make a unique contribution to patient management decisions in selected patient popula-tions.These groups include women with dense breasts, women with nonpalpable mammographically indeterminate lesionsϾ1cm,and women with palpable abnormalities. This multicenter study on563subjects with biopsy confirmation defined the diagnostic characteristics of planar 99m Tc-sestamibi breast imaging.The institutional sensitivity and specificity for breast cancer detection in palpable lesions were87%and76%and were61%and87%for nonpalpable lesions.The negative predictive value was94%in patients with a40%or lower mammographic likelihood of breast cancer.Sensitivity is independent of patient age,breast density,and mammographically established likelihood of malignancy but is decreased for small nonpalpable tumors. ACKNOWLEDGMENTSThe authors thank the patients and study coordinators who contributed to this study;the DuPont Pharmaceuticals Medical Research Staff,in particular Lori Bernard,MS, Edward Hogan,MS,Bernadette Emond,Rosemary Kerwin, RPh,Rommel Hidalgo,BS,and Tsushung A.Hua,PhD;and the blinded readers,core laboratory staffs,and principal investigators.The authors also express their appreciation to Mary Atkinson and Nancy Bush for their assistance in preparation of this manuscript.This study was supported by grants from DuPont Pharmaceuticals Company.This work was presented in part at the43rd Annual Meeting of the Society of Nuclear Medicine,Denver,CO,June3–5,1996. 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of201Tl and99m Tc-MIBI in HeLa cell[in Japanese].Kaku Igaku.1995;32:651–658.7.Packard AB,Kronauge JF,Limpa-Amara N,Lampson L,O’Tuama LA,Jones AG.Tumor uptake of99m Tc-MIBI and201Tl by a9L gliosarcoma brain tumor model in rats.Nucl Med Biol.1993;20:773–776.8.Otsuka N,Mimura H,Morita K,et al.Study on tumor accumulation property of99m Tc-HM-PAO and99m Tc-MIBI in rabbits bearing VX-2cancer[in Japanese].Kaku Igaku.1995;32:199–203.9.Steyn PF,Ogilvie G.99m Tc-methoxy-isobutyl-isonitrile(sestamibi)imaging ofmalignant canine lymphoma.Vet Radiol Ultrasound.1995;36:411–416.10.Crane PD,Onthank DC,Bourque CR,et al.Autoradiography and radioscintigra-phy of technetium-99m-sestamibi in c-neu transgenic mice.J Nucl Med.1995;36:1862–1868.11.Khalkhali I,Mena I,Jouanne E,et al.Prone scintimammography in patients withsuspicion of carcinoma of the breast.J Am Coll Surg.1994;178:491–497.12.Vicioso Jime´nez A,Man˜as Meron˜o E,Delgado Carreras JL,et al.Breastgammagraphy with MIBI-Tc99m in the assessment of 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I,et al.Technetium-99m-sestamibi scintigraphy ofbreast lesions:clinical and pathological follow-up.J Nucl Med.1995;36:1784–1789.19.Lu G,Shih W-J,Huang H-Y,et al.99Tcm-MIBI mammoscintigraphy of breastmasses:early and delayed imaging.Nucl Med Commun.1995;16:150–156.20.Palmedo H,Schomburg A,Gru¨nwald F,Mallmann P,Krebs D,Biersack HJ.Technetium-99m-MIBI scintimammography for suspicions breast lesions.J Nucl Med.1996;37:626–630.21.Breast Imaging Reporting and Data System(BI-RADS).Reston,V A:AmericanCollege of Radiology;1993.22.Fleiss JL.Statistical Methods for Rates and Proportions.New York,NY:JohnWiley&Sons;1981.23.Jackson VP,Hendrick RE,Feig SA,Kopans DB.Imaging of the radiographicallydense breast.Radiology.1993;188:297–301.24.Palmedo H,Biersack HJ,Lastoria S,et al.Scintimammography with technetium-99m methoxyisobutylisonitrile:results of a prospective European multicentre trial.Eur J Nucl Med.1998;25:375–385.25.Prats E,Carril JM,Herranz R,Meron˜o E,Banzo J.Spanish 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C-S ESTAMIBI B REAST I MAGING•Khalkhali et al.1979。

国际医学放射学杂志ＩｎｔＪＭｅｄＲａｄｉｏｌ２０20Nov 鸦43穴6雪：726-730促结缔组织增生性纤维母细胞瘤的影像诊断彭一檬1张春银2吴骥2王芳3李勇1【摘要】促结缔组织增生性纤维母细胞瘤（DF ）是一种罕见的良性软组织肿瘤，目前确诊主要依靠病理及免疫组化。

影像诊断多采用超声、X 线、CT 、MRI 及18F-FDG PET/CT 等技术，能够提供DF 的位置、大小、形状、密度、边缘以及与周围组织关系等信息。

其中，DF 的MRI 表现具有一定特征性，可根据T 2WI 低信号及病灶边缘强化征象与一般软组织肿瘤相鉴别。

就DF 的影像表现进行分析和总结，以利于提高对该病影像表现的认识。

【关键词】促结缔组织增生性纤维母细胞瘤；体层摄影术，X 线计算机；磁共振成像中图分类号：R445；R730.4文献标志码：AAdvances in imaging diagnosis of desmoplastic fibroblastomaPENG Yimeng 1,ZHANG Chunyin 2,WU Ji 2,WANGFang 3,LI Yong 1.1Department of Radiology,Suining Central Hospital,Suining 629000,China;2Department of Nuclear Medcine,Affiliated Hospital of Southwest Medical University;3Department of Ultrasound,Suining Central Hospital【Abstract 】Desmoplastic fibroblastoma (DF)is a rare benign soft tissue tumor,the definitive diagnosis now mainlydepends on pathological and immunohistochemical examinations.Imaging diagnosis is accomplished mostly by utilizing ultrasound,X-ray,CT,MRI,１８F-FDG PET/CT,and other technologies.Imaging exams can provide information about the location,size,shape,density,edge,and relationship with surrounding tissues of DF.The MRI manifestations of DF have certain characteristics,which is helpful to distinguish the general soft tissue from tumors based on T 2WI low signal and lesion edge enhancement signs.We reviewed the imaging manifestations of DF to improve the understanding of its imaging characteristics.【Keywords 】Desmoplastic fibroblastoma;Tomography,X-ray computed;Magnetic resonance imagingＩｎｔＪＭｅｄＲａｄｉｏｌ，２０20，43（6）：726-730作者单位：1遂宁市中心医院放射科，遂宁629000；2西南医科大学附属医院核医学科；3遂宁市中心医院超声科通信作者：李勇，E-ma ｉｌ：*****************DOI:10.19300/j.2020.L18036临床探究与评析促结缔组织增生性纤维母细胞瘤（ｄｅsmoplasticfibroblasto ｍａ，ＤＦ）又名胶原纤维瘤（ｃｏｌlagenousfibroma ，ＣＦ），２013年第4版WHO 软组织与骨肿瘤将其分类为“良性，纤维母细胞/肌纤维母细胞性肿瘤”[1-2]。

碧云天生物技术/Beyotime Biotechnology 订货热线：400-168-3301或800-8283301 订货e-mail ：****************** 技术咨询：***************** 网址：碧云天网站 微信公众号Cell Counting Kit-8 (CCK-8试剂盒)产品编号 产品名称包装 C0038Cell Counting Kit-8 (CCK-8试剂盒)500次产品简介：Cell Counting Kit-8，简称CCK-8试剂盒或CCK8试剂盒，是一种基于WST-8而广泛应用于细胞增殖和细胞毒性的快速、高灵敏度检测的试剂盒。

WST-8是一种类似于MTT 的化合物，在电子耦合试剂存在的情况下，可以被线粒体内的一些脱氢酶还原生成橙黄色的formazan (参考图1)。

细胞增殖越多越快，则颜色越深；细胞毒性越大，则颜色越浅。

对于同样的细胞，颜色的深浅和细胞数目呈线性关系。

图1. WST-8检测原理图 (EC=electron coupling reagent ，即电子耦合试剂)WST-8是MTT 的一种升级替代产品，和MTT 或其它MTT 类似产品如XTT 、MTS 等相比有明显的优点。

首先，MTT 被线粒体内的一些脱氢酶还原生成的formazan 不是水溶性的，需要有特定的溶解液来溶解；而WST-8和XTT 、MTS 产生的formazan 都是水溶性的，可以省去后续的溶解步骤。

其次，WST-8产生的formazan 比XTT 和MTS 产生的formazan 更易溶解。

再次，WST-8比XTT 和MTS 更加稳定，使实验结果更加稳定。

另外，WST-8和MTT 、XTT 等相比线性范围更宽，灵敏度更高。

WST-8和WST-1相比，检测灵敏度更高，更易溶解，并且更加稳定。

本试剂盒可以用于细胞因子等诱导的细胞增殖检测，也可以用于抗癌药物等对细胞有毒试剂诱导的细胞毒性检测，或一些药物诱导的细胞生长抑制检测。

Status epilepticus (SE), a condition characterized by persistent seizures presents a difficult clinical problem. While it is clear that major motor seizures can lead to permanent pathological damage and altered physiological function, the changes accompanying more focal discharges are less clear.1Epilepsia partialis continua is a form of SE characterized by continuous, well-localized, clonic, focal motor myotonias.Epilepsia partialis continua is notoriously refractory to anti-ABSTRACT:Background:Little is understood about the evolution of structural and functional brain changes during the course of uncontrolled focal status epilepticus in humans. Methods:We serially evaluated and treated a nine-year-old girl with refractory focal status epilepticus. Long-term EEG monitoring, MRI, MRA, SPECT, intraoperative visualization of affected cortex, and neuropathological examination of a biopsy specimen were conducted over a three year time span. Imaging changes were correlated with simultaneous treatment and EEG findings. Results:The EEG monitoring showed almost continuous spike discharges emanating initially from the right frontocentral area. These EEG abnormalities were intermittently suppressed by treatment with anesthetics. Over time,additional brain areas developed epileptiform EEG abnormalities. Serial MRI studies demonstrated an evolution of changes from normal, through increased regional T2 signal to generalized atrophy.An MRAdemonstrated dilatation of the middle cerebral artery stem on the right compared to the left with a broad distribution of flow-related enhancement. An 18FDG-PET scan showed a dramatically abnormal metabolic profile in the same right frontocentral areas, which modulated in response to treatment during the course of the illness. A right frontotemporal craniotomy revealed a markedly hyperemic cortical focus including vascular shunting. A sample of resected cortex showed severe gliosis and neuronal death. Conclusions:The co-registration of structural and functional imaging and its correlation with operative and pathological findings in this case illustrates the relentless progression of regional and generalized abnormalities in intractable focal status epilepticus that were only transiently modified by exhaustive therapeutic interventions.Increased flow through large vessels appeared to be shunted and did not translate into increased microvascular perfusion.RÉSUMÉ: Imagerie longitudinale multimodale du status épilepticus focal.Introduction : La compréhension de l’évolution des changements structuraux et fonctionnels pendant le status épilepticus focal dans le cerveau humain est très limitée. Méthodes : Nous avons effectué une évaluation sériée chez une fillette de neuf ans que nous suivons pour un status épilepticus focal réfractaire au traitement. Le monitorage ÉEG à long terme, l’IRM,l’ARM, la TEMP, la visualisation peropératoire du cortex atteint et l’examen neuropathologique d’un spécimen anatomopathologique ont été réalisés sur une période de trois ans. Les changements à l’imagerie étaient corrélés au traitement et aux observations à l’ÉEG. Résultats : Le monitorage ÉEG a montré des décharges de pointes émanant initialement de la zone fronto-centrale droite. Ces anomalies électroencéphalographiques étaient supprimées de façon intermittente par les anesthésiques. Avec le temps, des anomalies épileptiformes à l’ÉEG sont apparues dans d’autres régions du cerveau.L’IRM en série a montré une évolution des changements dans les zones initialement normales, soit d’un signal régional T2 augmenté à une atrophie généralisée. L’ARM a montré une dilatation du tronc de l’artère cérébrale moyenne du côté droit par rapport au gauche, avec une distribution large du rehaussement relié au flot. Un PETscan au 18FDG a montré un profil métabolique très anormal dans cette zone fronto-centrale droite qui était modulépar le traitement pendant l’évolution de la maladie. À la craniotomie fronto-temporale droite, on a observé un foyer cortical très hyperhémique avec dérivation vasculaire. Une biopsie du cortex a montré une gliose sévère avec mort neuronale. Conclusions : L’imagerie structurelle et fonctionnelle utilisée conjointement, en corrélation avec les observations chirurgicales et anatomopathologiques, illustrent la progression implacable des anomalies régionales. Elles se sont éventuellement généralisées chez cette patiente présentant un status épilepticus réfractaire au traitement, et n’étaient modifiées que temporairement par des interventions thérapeutiques exhaustives. L’accroissement du flot sanguin dans les gros vaisseaux semblait dévié et n’entraînait pas d’augmentation de la perfusion microvasculaire.Can. J. Neurol. Sci. 2004; 31: 276-281276THE CANADIAN JOURNALOF NEUROLOGICALSCIENCESMultimodal Longitudinal Imaging of Focal Status EpilepticusColin P. Doherty,Andrew J. Cole, P. Ellen Grant, Alan Fischman,Elizabeth Dooling, Daniel B. Hoch, Tessa Hedley White, G. Rees CosgroveFrom the Epilepsy Service, Neurology Service, (CPD, AJC, DBH); Department of Neuroradiology, (PEG); Nuclear Medicine Unit, Department of Radiology, (AF);Epilepsy Surgery Unit, Neurosurgical Service, (GRC); Pediatric Neurology,Department of Neurology, (ED); Department of Neuropathology, (THW)Massachusetts General Hospital and Harvard Medical School, Boston, USA.R ECEIVED A PRIL 28, 2003. A CCEPTED INFINALFORM N OVEMBER 17, 2003.Reprint requests to:Andrew J. Cole, MGH Epilepsy Service, VBK-830,Massachusetts General Hospital, Fruit Street, Boston, Massachusetts 02114 USACASE REPORTLE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUESVolume 31, No. 2 – May 2004277epileptic medical therapy but may respond better to subpial transection 2or resection. Epilepsia partialis continua is often a sign of a serious progressive brain disease, perhaps most commonly Rasmussen’s chronic encephalitis 1but in some cases no clear etiology is established. We present a case of persistent and continuous focal motor seizures, which fulfilled the criteria for epilepsia partialis continua. The evolution of multiple anatomic and functional imaging studies are discussed in light of intra-operative and pathological findings. C ASE REPORTA previously healthy nine-year-old left-handed girl presented initially to a local hospital with episodes of left facial twitching.Magnetic resonance imaging (MRI) was unremarkable, and she was treated with carbamazepine. Six months later she woke with unremitting twitching involving the left arm and face. She was admitted to a local hospital and required pentobarbital coma to control the events. Magnetic resonance imaging on admission and one week later were normal. She continued to have seizures after several attempts to wean from pentobarbital coma. On hospital day 14 she was transferred to thishospital. On arrival she was unconscious but breathing spontaneously on a respirator. Clinically obvious focal seizure activity affecting the left side was observed in episodes lasting 15 minutes every one to two hours (Figure 1). The EEG examination showed continuous sharp discharges occurring at 1 Hz arising from the right central region. An extensive biochemical, metabolic and infectious work-up failed to reveal a cause.Cerebrospinal fluid examination on two occasions showed no cells, total protein of 11 and 16 mg/dl, appropriate glucose levels, minimally elevated lactate (2.6 and 3.4 mmol/l, upper range of normal 2.2) and a normal electrophoresis pattern without oligoclonal bands. Bacterial,fungal and viral studies were negative. GluR3 antibodies were not detected in serum or CSF. Magnetic resonance imaging of the brain showed increased T2 signal in right hemisphere involving cortex,adjacent white matter and thalamus (Figure 2A). These changes were concordant with widespread metabolic abnormalities on 1 8f l u r o -2-deoxy-glucose positron emission tomography (18FDG-PET)(Figure 2B).A magnetic resonance angiogram (MRA) showed massive dilation of the right middle cerebral artery with increased flow related enhancement in the middle cerebral artery territory (Figure 2C). Single photon emitted computed tomography (SPECT) scan after injection with 99Tc-HMPAOFigure 3:Composite figure of imaging on day 28 of status epilepticus,one week after pentobarbital coma was initiated, two days before surgery.Axial FLAIR image showing improved signal change in right frontotemporal areas with only minimal subcortical hyperintensity remaining (2A). A 18FDG-PET from the same day scan showing improvement in abnormal uptake of radio-labeled glucose in right frontotemporal regions, now highly localized to motor cortex.Figure 1:22 Lead EEG, day 13 of status epilepticus showing generalized background slowing and continuous 1 Hz sharp discharges in the right central regions (C4) which were only occasionally associated with clinical seizure activity in the left arm and face.Figure 2: Composite figure of imaging on day 14 of status epilepticus. Axial fluid attenuated inversion re c o v e r y (FLAIR) image showing incre a s e d signal in cortical and white matter regions in right frontotemporal areas (2A). 1 8F D G -P E T scan showing i n c r eased uptake of radio-labeled glucose in the same right frontotemporal region (2B). An MR angiogram showing dilatation of the right middle cerebral artery branches presumably reflecting increased blood flow to the active cortex (2C).278was normal. After a week in a pentobarbital coma, repeat MRI demonstrated improvement of the T2 changes which were now almost resolved apart from mild subcortical hyperintensity (Figure 3A). There was a similar normalization of glucose uptake seen on an 18FDG-PET done the same day (Figure 3B). However, with every attempted wean from the drug-induced coma the seizures returned.Based on persistent focal epileptic discharge, poor response to medical treatment, and lack of a specific diagnosis a right fronto-temporal craniotomy with biopsy was undertaken. Once the dura was opened, the inferior portion of the motor strip displayed obvious hyperemia and arterialization of veins indicating massive local shunting of blood (Figure 4A). The inferior 4-cm hyperemic area of precentral gyrus was resected using bipolar cautery and suction. Multiple subpial transections were then performed in the superior portion of the motorstrip. These resulted in cessation of clinical seizure activity in her left face, hand and arm. Examination of resected cortex showed extensive neuronal death, cortical gliosis and some reactive astrocytosis in the subcortical white matter, but no specific pathological diagnosis was apparent. The general cortical architecture was preserved and the myelin pattern of the cortex and underlying white matter is normal. Specifically there was no perivascular cuffing, microglial nodules nor spongiform change to suggest Rasmussen’s encephalitis nor any extensive evidence of inflammation (Figure 4B).Seizures recurred 12 hours postoperatively, and over several days events began to manifest clinical and EEG signs of left hemispheric involvement as well as continuation of the previously described right hemisphere abnormalities. An MRI study, performed six days latershowed postoperative change with ongoing T2 prolongation, now alsoABFigure 6:T1 axial fast spin echo image of brain three years postoperatively, showing massive ex vacuo ventricular dilatation with generalized white and gray matter loss.Figure 4:A:Intra-operative photograph showing right motor strip exposed beneath the dura. Arrows delineate hyperemia along the motor strip. B:Pathological specimen of resected cortex. The slide shows thickened vessels, eosinophilic atrophied neurons (arrow) and astrocytes with swollen pink cytoplasm on hematoxylin eosin staining. Only rare lymphocytes and microglia are noted. There is no perivascular cuffing nor spongiform change to suggest Rasmussen’s encephalitis (Magnification 20x ).Figure 5:Composite imaging postoperatively and after resumption of seizure activity.Axial FLAIR image two months after the operation showing significant atrophy and widespread bilateral increased cortical and subcortical signal intensity (5A ). An 18FDG-PET scan from two weeks after operation showed widespread increases in radio-labeled tracer in bilateral occipital and frontotemporal regions (5B ).LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUESVolume 31, No. 2 – May 2004279appearing to a lesser degree in the left hemisphere at a time when ongoing seizure activity appeared to involve the right side of the body.The patient was placed in a pentobarbital coma again. A follow-up study done two months later showed the progressive nature of the process with generalized cerebral atrophy and multifocal areas of T2 prolongation consistent with independent focal seizures from both hemispheres (Figure 5A). The new focus of activity on the left was confirmed by left hemisphere abnormalities on concurrent 1 8F D G -P E T e x a m i n a t i o n (Figure 5B). Over the next six weeks several attempts to wean from drug-induced coma were made but the seizures invariably returned.Eventually on a combination of primidone, valproate and gabapentin,she was weaned off pentobarbital for the last time. She continued to remain refractory to medical treatment and was finally discharged to long-term care in a persistent vegetative state with intermittent independent seizure activity affecting both sides of her body, which continues to this day.A final imaging study, done three years after presentation, demonstrates near complete loss of cortical volume with massive compensatory dilatation of the ventricular system (Figure 6).D ISCUSSIONThis case documents the evolution of imaging findings during a catastrophic course of persistent and intractable focal SE. We demonstrate a clear correlation between the clinical,neurophysiological, intra-operative, and functional and anatomic imaging findings. Key findings include the correlation of functional imaging abnormalities with disease activity and anatomic changes, the striking increase in local bloodflow, and the lack of a primary pathological diagnosis. These findings suggest that some cases of focal SE are idiopathic, in the original sense of the word, “disease of the self”. While animal studies of the effects of prolonged status are well-described, the effects on the human brain of such a catastrophic course are not well-understood.1,3In the last 20 years, nuclear imaging studies such as SPECT and PET using both 18fluro-2-deoxy-glucose and 15oxygen have been used to noninvasively localize seizure foci through the analysis of ictal bloodflow and interictal metabolism (see Spencer for review 4). Despite these studies, little is understood about the dynamics of flow in the microcirculation. Some evidence from animal studies suggests that there is uncoupling of metabolism and blood flow in focal seizures with the requirements of metabolism often outstripping the delivery of oxygenated blood.5On the other hand evidence from human studies suggests that in fact perfusion outstrips metabolic demand.6In 1933, Penfield 7described evidence of increased local blood flow in the ictal zone during and after seizure activity:After the attack the cerebral arteries pulsate violently …Their color becomes a bright red and arteries which were not seen to pulsate before the seizure may now begin to do so visibly. In fact this recovery may go so far that the veins themselves take on an arterial hue.7This dramatic 70-year-old description is uncannily similar to the gross operative findings in this case.Advances in structural imaging have further supplemented functional localization in SE. Neuroimaging of the brain directly after prolonged epileptic seizures, either focal or generalized,may reveal focal cerebral abnormalities that are typicallytransient. Cerebral hypodensities that enhance with contrast on computed tomography (CT) have been reported since 1980.8In most cases the changes suggested the development of focal cerebral cytotoxic edema. By the early 1990s, reports of T2hyperintensity changes in focal areas associated with SE on MRI began appearing in the literature.8-18A variety of metabolic events which lead to edema have been invoked to explain the changes including cytotoxic edema due to swelling of glial cells,increases in intracellular sodium concentration secondary to Na/K pump failure 19and vasogenic edema caused by excessive glutamate release.12There are several imaging features in this case that merit discussion. Firstly the initial imaging study, obtained six months prior to the onset of status was normal, as was an MRI obtained a week after onset of SE. Widespread regional T2 changes first appeared a full two weeks after SE began and were concordant with both EEG and metabolic abnormalities on 18FDG-PET. By contrast, perfusion at the microvascular level as assessed by 99TC-HMPAO-SPECT remained normal. We hypothesize that the increased blood flow visualized by MRA was due to increased arterio-venous shunting as visualized intraoperatively.Magnetic resonance angiogram changes of this nature have been reported in only one patient previously.12The attenuation of the T2 and the metabolic abnormalities during pentobarbital coma has not been reported previously nor has concordance of these T2 changes with visualized arterialization of surface veins and hyperemia in the same area at craniotomy. Unlike previous reports in which the T2 changes tended to resolve, favoring the cytotoxic edema hypothesis, the changes in this case persisted for months after the onset of status presumably reflecting the development of dense gliosis and neuronal death as demonstrated neuropathologically. To g e t h e r , our findings suggest that cerebrovascular responses to SE in this patient,which appeared to be largely microvascular, were insufficient to adequately supply local neuronal demand, contributing to cell death.Perhaps the most dramatic structural finding in this case was the relentless progressive generalized brain atrophy over the course of the illness. The literature in this area includes detailed descriptions of progressive focal atrophy on serial MRIs after SE in mesial structures.14,20Similarly in more intractable disease such as epilepsia partialis continua secondary to Rasmussen’s encephalitis, atrophy is extensive but appears limited to the a f fected hemisphere.2 1The explanation for the widespread atrophy in our patient is not clear.The role of three weeks of intravenous dexamethasone in generalized brain atrophy in this case must be considered, but the degree of atrophy in combination with previous experience with steroid treatment in other disease states suggests that additional factors must have contributed to the development of widespread atrophy. A t present we cannot differentiate between the roles of numerous biochemical consequences of repeated seizures such as ionic fluxes, kinase activation, early and late gene expression, protein expression and modification, synaptic reorganization, the roles of indirect consequences of seizures such as local hypoxia,hypotension, and acidosis (see Cole 3for review).Catastrophic epilepsy arising in childhood may be due to structural, infectious or metabolic disturbances. Structural abnormalities include cortical dysgenesis, congenitalTHE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES280demyelinating disease, and vascular insults such as venous occlusion, anoxic injury and major trauma. Infectious etiologies include viral encephalitis, focal or multifocal cerebritis, and perhaps chronic encephalitis (Rasmussen’s disease), although no causative agent has been identified, and recent studies have suggested a potential autoimmune basis for the latter. Metabolic disorders as a cause of catastrophic seizures are generally described in terms of seizure types such as childhood encephalopathy with myoclonus and myoclonic–astatic seizures (see Shields 22for discussion). Recently there have been a number of case reports of rare metabolic disorders engendering severe intractable seizures, including Alpers syndrome,2 3,24selenium deficiency,2 5peroxisomal disease,2 6g l u t h a t h i o n e synthetase deficiency,27glucose transporter deficiency syndrome and sulphite oxidase deficiency.28Most of these were identified in association with infantile seizures soon after birth rather than in later childhood. These protean conditions demonstrate that while there is no single etiology for, nor common pathological abnormality in catastrophic epilepsy arising in childhood, all of these conditions are associated with a poor neurological outcome. The presence of epilepsia partialis continua appears to confer a particularly poor prognosis regardless of the cause.29Large case series of catastrophic childhood epilepsy are rare.The natural history of Rasmussen’s encephalitis has been recently documented in a longitudinal study of 16 patients demonstrating typical neuroradiographic features and also a subgroup of slightly older patients who may have a slight better prognosis.30In a study of 15 children without Rasmussen’s encephalitis, although it was possible to classify the patients with respect to seizure localization, either multi-focal or lateralized,the outcome in all cases was poor.24Of the 15 cases, only eight had a unifying diagnosis. Three had the Alpers syndrome, three were thought to have cerebral dysgenesis, one had anoxic damage, one had congenital cytomegalovirus, and seven patients had no specific diagnosis. Other efforts at defining the syndrome of catastrophic epilepsy by seizure phenomenology have been equally unrevealing. Coppola 31described an epileptic condition in a number of patients characterized by intractable focal seizures and poor intellectual outcomes. Inclusion in the group required an unidentified cause, but the coining of term “malignant developmental arrest” may have been the most useful contribution. In those that do have a common identifiable cause such as acquired cortical damage, knowledge of the etiology appears to have little impact on the course of the disease. In a retrospective review of catastrophic epilepsy in 42 patients with a history of encephalitis, only a small subset of those with seizures localized by EEG to one temporal lobe appeared to have a favourable prognosis.32Recent guidelines for evaluating patients with catastrophic epilepsy have concentrated on imaging in an effort to identify localized abnormalities such as cerebral dysgenesis so that either focal cortical resection or hemispherectomy may be added to the treatment options. This approach is based on follow-up studies of small numbers of surgical patients with catastrophic seizures who have had sustained periods of seizure freedom and even demonstrated a tendency to “catch-up” developmentally if operated on early enough.33In our case the etiology remains obscure. The biochemical and metabolic evaluation was negative. The neuropathologicalexamination of the biopsy specimen did not reveal a specific diagnosis, although it was taken from the center of the most consistently involved cortical region and included surrounding tissue and subcortical white matter. Detailed examination revealed only evidence of cell death and gliosis, with no indication of cerebral dysgenesis, inflammatory changes, viral inclusions or tumor.While it is possible that subtle dysgenesis could have been missed, especially after considerable neuronal loss had occurred, no evidence of a structural abnormality was apparent on MRI prior to the development of seizure-related structural changes. We suggest that SE in this patient was indeed idiopathic in the strict sense of the word, that is a consequence of some unique constellation of activity, connectivity, and stimulation in this individual’s brain that resulted in destabilization of the normal neuronal network architecture. This view, which is conjectural, is proposed as a hypothesis that might be tested using techniques of computational modeling.This detailed case study of the catastrophic course of epilepsia partialis continua in a child reveals several intriguing associations. The employment of structural and functional imaging illustrates the tight correlation of abnormal electrical,metabolic activity and the visualized cortical blood flow.Furthermore, the development of local and generalized structural and metabolic changes were only transiently affected by a range of therapies demonstrating the relentless progressive nature of the damage caused by such constant activity.A CKNOWLEDGEMENTSWe thank the patient and her family for their cooperation and the medical and surgical staff at Massachusetts General Hospital for their care over the course of the patient’s illness.R EFERENCES1. Wasterlain C, Fujikawa D, Penix L, Sankar R. Pathophysiologicalmechanisms of brain damage from status epilepticus. Epilepsia 1993; 34: S37-S53.2. Molyneux P, Barker R, Thom M, et al. Successful treatment ofintractable epilepsia partialis continua with multiple subpial transsections. JNNP1998; 65: 137-138.3. Cole A. Is epilepsy a progressive disease? The neurobiologicalconsequences of epilepsy. Epilepsia 2002; 41(Suppl 2): S13-S22.4. Spencer S, Bautista E. Functional neuroimaging in localization ofthe ictal onset zone. In: Henry T, Duncan J (Eds.) Functional Imaging in the Epilepsies, Philadelphia: Lippincott Williams and Wilkins, 2000: 285-296.5. Bruehl C, Hagemann G, Witte O. Uncoupling of blood flow andmetabolism in focal epilepsy. Epilepsia 1998; 39: 1235-1242.6. Franck G, Sadzot B, Salmon E, et al. Regional cerebral bloodflowand metabolic rates in human focal epilepsy and status epilepticus. Adv Neurol 1986; 44 : 935-948.7. Penfield W.The evidence of a cerebral vascular mechanism inepilepsy.Ann Intern Med 1933; 7: 303-310.8. Henry T, Drury I, Brunberg J, et al. Focal cerebral magneticresonance changes associated with partial status epilepticus.Epilespia 1994; 35: 35-41.9. Callahan D, Noetzel M. Prolonged absence status epilepticusassociated with carbamazepine therapy, increased intracranial pressure and transient MRI abnormalities. Neurology 1992; 42:2198-2201.10. Fazekas F, Kapeller P, Schmidt R, et al. Magnetic resonanceimaging and spectroscopy findings after focal status epilepticus.Epilepsia 1995; 36: 946-949.11. Kramer R, Luders H, Lesser R, et al. Transient focal abnormalitiesLE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUESVolume 31, No. 2 – May 2004281of neuroimaging studies during focal status epilepticus. Epilepsia 1987; 28: 528-532.12. Lansberg M, O’Brien M, Norbash A, et al. MRI abnormalitiesassociated with partial status epilepticus. Neurology 1999;52:1021-1027.13. Lazeyras F, Blanke O, Zimine I, et al. MRI, 1H-MRS, andfunctional MRI during and after prolonged non-convulsive seizure activity. Neurology 1999; 55: 1677-1682.14. Meierkord H, Wieshmann U, Niehaus L, Lehmann R. Structuralconsequences of status epilepticus demonstrated with serial magnetic resonance imaging. Acta Neurologica Scadinavica 1997; 96: 127-132.15. Najm I, Wang Y, Shedid D, et al. MRS metabolic markers ofseizures and seizure-induced neuronal damage. Epilepsia 1998;39: 244-250.16. Riela A, Sires B, Penry J. Transient magnetic resonance imagingabnormalities during partial status epilepticus. J Child Neurol 1991; 6:143-145.17. Wieshmann U, Woermann F, Lemieux L, et al. Development ofhippocampal atrophy: a serial magnetic resonance imaging study in a patient who developed epilepsy after generalized status epilepticus. Epilepsia 1997; 38: 1238-1241.18. Yaffe K, Ferriero D, Barkovich J, Rowley H. Reversible MRIabnormalities following seizures. Neurology 1995; 45: 104-108.19. Zhong J, Petroff O, Prichard J. Barbiturate-reversible reduction ofwater diffusion coefficient in flurothyl-induced status epilepticus in rats. Magn Reson Med 1995; 33: 253-256.20. Nohria V , Lee N, Tien R, et al. Magnetic resonance imagingevidence of hippocampal sclerosis in progression: a case report.Epilepsia 1994; 35: 1332-1336.21. Bien C, Urbach H, Deckert M, et al. Diagnosis and staging ofR a s m u s s e n ’s encephalitis by serial and histopathology.Neurology 2002; 58: 250-257.22. Shields WD. Catastrophic epilepsy in childhood. Epilepsia 2000;41(Suppl 2):S2-S6.23. Gauthier-Villars M, Landrieu P, Cromier-Daire V, et al. Respiratorychain deficiency in Alpers syndrome. Neuropediatrics 2001;32:150-152.24. Ishii K, Oguni H, Hayashi K, et al. Clinical study of catastrophicinfantile epilepsy with focal seizures. Pediatr Neurol 2002; 27:369-377.25. Ramaekers VT, Calomme M, Vanden Berghe D, Makropoulos W.Selenium deficiency triggering intractable seizures.Neuropediatrics 1994; 25:217-223.26. Takahashi Y, Suzuki Y , Kumazakai K, et al. Epilepsy in peroxisomaldiseases. Epilepsia 1997; 38:182-188.27. Ristoff E, Mayatepek E, Larsson A. Long-term clinical outcome inpatients with glutathione synthetase deficiency. J Pediatr 2001;139:79-84.28. Slot HM, Overweg-Plandsoen W, Bakker HD, et al. Molybdenum-cofactor deficiency: an easily missed cause of neonatal convulsions. Neuropediatrics 1993; 24:139-142.29. Baram TZ, Mitchell WG, Snead OC. Prognostic significance ofacute epilepsia partialis continua. Pediatr Neurol 1991; 7(2): 144-146.30. Bien CG, Widman G, Urbach H, et al. The natural history ofRasmussen’s encephalitis. Brain 2002; 125(8): 1751-1759.31. Coppola G, Plouin P, Chiron C, Robain O, Dulac O. Migratingpartial seizures in infancy: a malignant disorder with develop-mental arrest. Epilepsia 1995; 36:1017-1024.32. Trinka E, Dubeau F,Andermann F, et al. Clinical findings, imagingcharacteristics and outcome in catastrophic post-encephalitic epilepsy. Epileptic Disord 2000; 2(3):153-162.33. Wyllie E. Surgery for catastrophic localization-related epilepsy ininfancy. Epilepsia 1996; 37(Suppl 1): S22-S25.。

原发性胰腺淋巴瘤的CT、MRI和PET/CT表现陈伯柱1，孙双双1，仇毓东2，伏旭2，史炯3，唐敏1*1.南京大学医学院附属鼓楼医院医学影像科，江苏南京210008；2.南京大学医学院附属鼓楼医院胆胰外科，江苏南京210008；3.南京大学医学院附属鼓楼医院病理科，江苏南京210008；*通信作者唐敏【摘要】目的总结原发性胰腺淋巴瘤（PPL）的CT、MRI和PET/CT表现，提高对本病的认识。

资料与方法回顾性分析2017年1月—2021年12月南京大学医学院附属鼓楼医院4例PPL的临床及影像资料。

患者均行胰腺CT平扫及增强扫描、上腹部MRI 及全身PET/CT检查。

重点分析病灶的部位、大小、形态、强化方式、周围血管情况、信号特点、胰胆管改变、累及范围，并测量病灶的最大标准化摄取值。

结果4例患者中腹痛2例，黄疸1例，体检发现1例。

发生于胰头3例，病灶长径5.2~11.4 cm。

CT平扫呈低密度，MRI呈稍长T1稍长T2信号，扩散加权成像明显弥散受限，病灶轻中度均匀强化，1例出现坏死囊变，4例病灶均包绕周围血管，包绕动脉未见明显狭窄，受累静脉狭窄2例。

PET/CT均为明显高代谢灶，最大标准化摄取值为9.2~21.3。

术前影像正确诊断2例，误诊为胰腺癌1例、肿块性胰腺炎1例。

结论PPL的影像学表现具有一定特征，加深对其影像学表现的认知可减少误诊。

【关键词】胰腺肿瘤；淋巴瘤；磁共振成像；体层摄影术，X线计算机；体层摄影术，发射型计算机【中图分类号】R735.9；R733.4；R445 【DOI】10.3969/j.issn.1005-5185.2023.11.008CT, MRI and PET/CT Findings of Primary Pancreatic LymphomaCHEN Bozhu1, SUN Shuangshuang1, QIU Yudong2, FU Xu2, SHI Jiong3, TANG Min1*Department of Medical Imaging, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University, Nanjing 210008,【Abstract】Purpose To summarize the CT, MRI and PET/CT findings of primary pancreatic lymphoma (PPL). Materials and Methods The clinical and imaging data of four patients with pathologically confirmed PPL from January 2017 to December 2021 in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University were retrospectively reviewed. All four patients underwent pancreatic CT plain and enhanced scans, upper abdominal MRI examinations, and whole-body PET/CT examinations. We mainly focused on the location, size, morphology, enhancement pattern, involvement of peripheral blood vessels, signal characteristics, cholangiopancreatography changes and extent of the lesion. Besides, we also measured the maximum standardized uptake value of the lesion. Results These four patients, symptoms included abdominal pain (two cases) and jaundice (one case) and one case showed no symptoms and was found during imaging examination. The masses, ranging from 5.2 to 11.4 cm, were mainly located in the pancreatic head (three cases). All cases showed low density on CT plain scan. On MRI, the masses showed slightly low intensity T1 and slightly high intensity T2, and obvious diffusion restriction. All masses showed slight to moderate enhancement, only one case showed necrosis. Of four cases with vascular embedding, there were two cases with venous stenosis. On PET/CT, all masses showed hypermetabolism with maximum standardized uptake value ranging from 9.2 to 21.3. Two cases were preoperatively diagnosed with accuracy as pancreatic lymphoma, while one case was misdiagnosed as pancreatic cancer and one case as focal pancreatitis. Conclusion Imaging findings of PPL have certain characteristics, increased awareness of these findings may reduce misdiagnosis.【Key words】Pancreatic neoplasms; Lymphoma; Magnetic resonance imaging; Tomography, X-ray computed; Tomography, emission-computedChinese Journal of Medical Imaging, 2023, 31 (11): 1168-1171原发性胰腺淋巴瘤（primary pancreatic lymphoma，PPL）是起源于胰腺、主体位于胰腺区域的结外淋巴瘤，可伴有邻近淋巴结受累及远处播散[1]。

Carbon monoxide poisoningThe deadly effect of carbon monoxide was known as long ago as Greek and Roman times, when the gas was used for executions. In 1857 Claude Bernard postulated that its noxious effect was caused by reversible displacement of oxygen from haemoglobin to form carboxyhaemoglobin. In 1926 it became apparent that hypoxia was caused not only by deficient oxygen transport but also by poor tissue uptake. Warberg used yeast cultures to show that cellular uptake of oxygen was inhibited by exposure to a large amount of carbon monoxide.Carbon monoxide is known as the silent killer since it has no colour or smell. Each year in Britain about 50 people die and 200 are severely injured by carbon monoxide poisoning4. Some poisonings are caused by self-harm but most are accidental. It is the commonest cause of accidental poisoning and, according to one estimate, as many as 25000 people in the UK have symptoms due to faulty gas appliance. In the 1960s and 1970s the conversion from coal gas to carbon-monoxide-free natural gas caused a dramatic reduction in poisoning. In this review I discuss modern approaches to management and preventionSOURCESCarbon monoxide is produced endogenously in small amounts as a byproduct of haem catabolism. Together with nitric oxide it affects cellular function and acts as a neurotransmitter. Environmental carbon monoxide is produced by incomplete combustion of any carboncontaining fuel (coal, petroleum, peat, natural gas). In Britain most accidents arise through central heating faults. By contrast, in the USA most deaths are caused by inhalation of exhaust fumes. In the United Kingdom car exhaust emissions of carbon monoxide have been reduced by catalytic convertors in all new cars. Surprisingly, when deaths occur in garages there have usually been open doors and windows9. There are even reports of poisoning occurring from carbon monoxide inhalation in the open air. Methylene chloride (paint stripper) fume inhalation is a rare cause of poisoning. In the liver it is converted to carbon monoxidePATHOPHYSIOLOGYCarbon monoxide has 210 times greater affinity for haemoglobin than oxygen. A small environmental concentration will thus cause toxic levels of carboxyhaemoglobin. After the carbon monoxide has selectively bound to haemoglobin the oxygen-haemoglobin dissociation curve of the remaining oxyhaemoglobin shifts to the left, reducing oxygen release .The affinity of carbon monoxide for myoglobin is even greater than for haemoglobin. Binding to cardiac myoglobin causes myocardial depression, hypotension and arrhythmias. Cardiac decompensation results in further tissue hypoxia and is ultimately the cause of death.Carbon monoxide shifts the oxygen-haemoglobin saturation curve to the left and changes it to a more hyperbolic shape. Less oxygen is available for the tissues. Shown is the oxygen diffusion gradient difference at 50% saturation.Cellular uptake of oxygen is blocked by binding of carbon monoxide with mitochondrial cytochrome aa3. The hypoxia precipitates endothelial cell and platelet release of nitric acid, which forms the free radical peroxynitrate. In the brain this causes further mitochondrial dysfunction, capillary leakage, leukocyte sequestration andapoptosis. The pathological changes occur mainly during the recovery (reperfusion) phase when lipid peroxidation (degradation of unsaturated fatty acids) occurs. The net result is reversible demyelination in the brain. Such changes are clearly evident on magnetic resonance imaging. Carbon monoxide has a predilection for ‘watershed’ areas of the brain where there is a meagre blood supply. The basal ganglia, with their high oxygen consumption, are most often affected. Other commonly affected areas are the cerebral white matter, hippocampus and cerebellum.CLINICAL SIGNS AND DIAGNOSISThe signs of carbon monoxide poisoning vary with concentration and length of exposure. Subtle cardiovascular or neurobehavioural effects occur at low concentrations. Lengthy exposure or acute exposure to high concentrations often causes coma and death. The onset of chronic poisoning is usually insidious and easily mistaken for 'flu, depression, food poisoning or in children gastroenteritis. Other family members may have a similar illness.The most common symptoms are headache, nausea and vomiting, dizziness, lethargy and a feeling of weakness. Infants may be irritable and feed poorly. Neurological signs include confusion, disorientation, visual disturbance, syncope and seizures. In acute poisoning, common abnormalities of posture and tone are cogwheel rigidity, opisthotonus and flaccidity or spasticity. Adults with coronary heart disease may experience angina, arrhythmias and myocardial infarction. Retinal haemorrhages and the classic cherry red skin colour are seldom seen. Other organs such as the kidney, liver and pancreas are rarely affected. A rise in creatine phosphokinase follows muscle necrosis. Hypoxaemia causes lactic acidaemia. Carbon monoxide poisoning is diagnosed by measuring carboxyhaemoglobin in a heparinized blood sample (arterial or venous. Symptoms usually begin when the concentration rises above 10%. There is a poor correlation between the blood level and the clinical condition. Symptoms reflect the dissolved concentration, which may be low in the face of a high carboxyhaemoglobin. In general, levels below 40% are not associated with coma or death. In a normal non-smoker the average is about 1%, rising to 15% in a heavy smoker. Levels of 5% are found in haemolytic anaemias and pregnancy. Pulse oximeters are not suitable for the diagnosis of carbon monoxide poisoning. The wavelength of most cannot distinguish between oxyhaemoglobin and carboxyhaemoglobin. A carbon monoxide breathalyser is a simple bedside screening test but its practical value is limited by numerous confounders such as smoking and alcoholThe fetus is particularly vulnerable to carbon monoxide poisoning. Fetal haemoglobin shifts the oxygen-haemoglobin dissociation curve to the left. Chronic exposure to carbon monoxide in pregnancy causes growth retardation, fetal distress and death. Survivors may have developmental disorders and brain damage. The risk is compounded by smoking in pregnancy. In the first months of infancy, while fetal haemoglobin remains raised, the risk is greater. People with sickle cell anaemia and thalassaemia who have a raised fetal haemoglobin are likewise at excess risk.TREATMENT AND PROGNOSISThe mainstay of treatment is 100% oxygen administration until the carboxyhaemoglobin level is normal. On this regimen the half-life of carboxyhaemoglobin is 74 minutes (compared with 320 minutes breathing air. Lactic acidosis facilitates tissue oxygen diffusion and should not be corrected unless extreme (pH<7.15). When the patient is stable enough to be transported, hyperbaric oxygen should be considered. This treatment is safe and well tolerated, the main complication being ear barotrauma. The decision about hyperbaric oxygen will often depend on ease of access to a hyperbaric facility.Hyperbaric oxygen has many benefits. The half-life of carboxyhaemoglobin at 3 ATA (absolute atmospheres) of oxygen is only 23 minutes. Other benefits are improved mitochondrial function, impairment of platelet adhesion in the capillaries and inhibition of lipid peroxidation12. But contrary to expectation, clinical trials of hyperbaric oxygen have given conflicting results. A recent Cochrane review of three major randomized controlled trials concluded that there is as yet no evidence of neurological benefit at one month. Ongoing trials will soon provide further information. In the absence of firm evidence most centres continue using hyperbaric oxygen if the carboxyhaemoglobin is above 25-30%. Myocardial ischaemia and neurological signs, especially coma, are treated with hyperbaric oxygen irrespective of the concentration. There is general agreement that prolonged hyperbaric oxygen is the treatment of choice in pregnancy. This is because fetal carboxyhaemoglobin is higher and clearance slower than in the mother. Carbon monoxide poisoning is unique in that neuropsychiatric signs can appear insidiously weeks after the patient appears to have recovered. These signs, which are most common in the elderly, occur within a month in 10-30%. Some of the frank neurological signs such as parkinsonism are easily detected. Personality, cognitive and memory changes are not readily apparent and can be missed unless specifically targeted. Children may present with behaviour or education problems. Most neuropsychiatric signs resolve within a year. In one study, review at 3 years revealed persistent signs in 11% There is no means of predicting recovery. However, patients with permanent signs are likely to have presented in comaPREVENTIONPublic education about the danger of carbon monoxide, with emphasis on safety in the home and workplace, is the key to effective prevention. Professional education targeted at community workers is also needed. This could be achieved through a media campaign when risk is greatest, during the winter. Because of the high incidence of gas-related poisoning, there is a role for the gas industry in public education. Close liaison between public health physicians and leaders of the building, gas and home heating industries is a prerequisite for an effective prevention strategy. Such collaboration ensures safety through proper standards for home ventilation, central heating installation and maintenance. Cheap batteryoperated carbon monoxide detectors are now widely available. They should be installed in new homes and in buildings such as garages where workers are at risk from exhaust fumes. In old properties, particularly where there is solid fuel heating, carbon monoxide detectors should be located in sleeping areas. In Britain only BSI standard detectors should be installed. In the USA, where detectors are mandatory in some cities, their value in preventing home poisoning has been well demonstrated.。