CASE REPORT
Acute Aortic Dissection With Carotid and Coronary Malperfusion From Imaging to Pathology Christelle Lardi, MD,* Johannes-Alexander Lobrinus, MD,Þ Francesco Doenz, MD,þ Tony Fracasso, MD, PD,* Marc Augsburger, PhD,*§ Patrice Mangin, MD, PhD,*§ and Silke Grabherr, MD, PD§ Abstract: Postmortem imaging, including postmortem computed tomography angiography, has become an integral tool in forensic investigation in recent years. A relatively new technique, multiphase postmortem computed tomography angiography, allows detailed visualization of the vascular system and makes it possible to evaluate the dynamic perfusion of aortic branches, including the coronary arteries. Here, we report a case of aortic dissection involving the ascending aorta (type A) with coronary and carotid malperfusion. This case illustrates the complementary use of many of the diagnostic tools that are now available in forensic practice, from imaging to conventional autopsy to pathologic techniques such as immunohistochemistry. Key Words: forensic imaging, postmortem angiography, aortic dissection, malperfusion
forensic radiographers.13 The combination of postmortem imaging and conventional autopsy can even be considered to be the new criterion standard for forensic investigation.1 Here, we present a case that illustrates how many of the diagnostic tools that are now available in forensic practice could be complementarily used to establish the cause of death. We present a case of an acute aortic type A dissection, according to the Stanford classification, and show how imaging and autopsy, used together, revealed the extent of the dissection in several aortic branches. We also show that only postmortem angiography could detect a dynamic complication that led to death in a case of coronary malperfusion generated by the dissection of the aortic wall. We also investigated the use of immunohistochemistry to evaluate early ischemic myocardium injury.
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n the past decade, forensic research teams all over the world have begun to use postmortem imaging in their analyses.1Y4 Especially in Switzerland,5,6 England,7,8 and Japan,4,9 such teams have worked to develop postmortem computed tomography (CT) angiography techniques. Postmortem CT angiography5,10,11 is a minimally invasive approach that allows very accurate and detailed investigation of the vascular system and thus helps the forensic team to detect vascular lesions. Using a standardized protocol developed recently, very high quality postmortem CT angiographies of the whole body can be performed in 1 hour.12 Multiphase postmortem CT angiography (MPMCTA) includes 1 native CT scan plus 3 angiographic phases (ie, arterial, venous, and dynamic phases). Using MPMCTA, we will discuss the possibility of detecting dynamic perfusion problems that are invisible using only native CT. At the University Center for Legal Medicine in Lausanne, Switzerland, MPMCTA is performed before classic autopsy as part of the routine investigation of cases in which there is a suspicion of vascular lesions. The images are then correlated with conventional autopsy findings. Both the standardized protocol and the entire radiologic examination can be carried out by Manuscript received October 2, 2013; accepted December 1, 2013. From the *University Center of Legal Medicine Lausanne-Geneva, Geneva University Hospitals; †Department of Pathology, Geneva University Hospitals, Geneva; ‡Department of Diagnostic and Interventional Radiology, University Hospital of Lausanne; and §University Center of Legal Medicine Lausanne-Geneva, University Hospital of Lausanne, Lausanne, Switzerland. This study was funded by the Promotion Agency for Innovation of the Swiss Confederation (KTI Nr.10221.1 PFIW-IW) and by the Fondation Leenaards, Lausanne, Switzerland. The authors report no conflicts of interest. Reprints: Christelle Lardi, MD, University Center of Legal Medicine Lausanne-Geneva, Geneva University Hospitals, Michel-Servet 1, CH-2011 Geneva 4, Switzerland. E-mail: [email protected]. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0195-7910/14/3503Y0157 DOI: 10.1097/PAF.0000000000000098
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CASE REPORT We report the case of a 61-year-old man who was found dead in his bed by his wife 1 morning. The emergency staff called to the site confirmed his death and did not initiate resuscitation measures. The victim had received regular medical checkups after undergoing liver transplantation 10 years before. He also had known general cardiovascular problems (hypertension and stroke) as well as chronic renal insufficiency.
Native CT Scan Before any manipulation of the corpse, a native CT scan was carried out around 46 hours since death using an 8-row CT unit (CT LightSpeed 8; GE Healthcare, Milwaukee, Wis) using the following scan parameters: field of view (FOV), 50 cm; slice thickness, 2.5 mm; interval of reconstruction, 2 mm, 1 mm; 120 kilovolt (peak) kV(p); 280 mA, 300 mA; and noise index, 15. The images obtained using native CT were viewed immediately by a forensic pathologist who was experienced in forensic imaging. They revealed the presence of extended vascular calcification and a flap of the vascular wall in the aortic arch. There was thus a suspicion of an aortic dissection, and the forensic pathologist in charge of the case decided to perform an MPMCTA. This examination was immediately carried out during the following hour.
External Examination The external examination, which was performed by the forensic pathologist in charge of the case, did not reveal any major traumatic lesions. There were several bruises of different ages on his back, thorax, and limbs, as well as some puncture/ injection sites related to the man’s recent hospitalization. The man was slightly overweight, with a body mass index of 26 (weight, 73 kg; height, 167 cm).
Collection of Postmortem Liquid Samples Samples for toxicological analyses, that is, peripheral and cardiac blood, urine, vitreous humor, and cerebrospinal fluid, were www.amjforensicmedicine.com
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collected under CT guidance (for urine and cardiac blood) by a forensic radiographer as described by Schneider et al.13 Urine was collected in a glucose urine tube. Vitreous humor and cerebrospinal fluid were sampled in a neutral serum tube and a glucose tube for postmortem biochemistry. Other fluids such as gastric contents and pericardial fluid were collected during conventional autopsy.
Multiphase Postmortem CT Angiography According to the standardized protocol described by Grabherr et al,12 cannulation of the femoral vessels was performed on 1 side using cannulas with a diameter of 16F for arteries and 18F for veins (MAQUET Gmbh & Co. KG, Rastatt, Germany). During the cannulation process, blood samples were collected in different tubes for toxicological and biochemical analysis. A recently developed pressure-controlled perfusion device (Virtangio; Fumedica AG) was used to inject a mixture of iodated contrast agent (6% of Angiofil; Fumedica AG, Switzerland) with paraffin oil (paraffinum liquidum, obtained from the local pharmacy). The arterial phase of MPMCTA was carried out using the following scan parameters: FOV, 50 cm; reconstructed slice thickness, 1.25 mm; reconstruction interval, 0.6 mm; 120 kV(p); and 280 mA. Scan parameters for the venous and dynamic phase were as follows: FOV, 50 cm; reconstructed slice thickness, 2.5 mm; reconstruction interval, 1.2 mm; 120 kV(p); and 280 mA.
Radiologic Interpretation All images were interpreted in a consensus reading by 2 board-certified radiologists (1 specialized in vascular radiology and 1 specialized in neuroradiology) and by 1 board-certified forensic pathologist who was trained in forensic imaging. A postmortem radiologic report was prepared that described all findings from native CT and from each phase of the MPMCTA.
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Three-dimensional volume-rendered (VR) images were only used for better visualization of the present communication. The native CT scan mainly showed severe calcification of the aorta and its major branches. The 3 coronary arteries and the aortic valve were particularly involved. An aortic dissection of both ascending and descending part of the aorta was suspected. Multiphase postmortem CT angiography could then confirm the diagnosis and demonstrate the presence of an aortic wall dissection that started from the ascending aorta and progressed to the abdominal aorta and which included both carotid arteries as well as the right renal artery (Figs. 1 and 2). Dissection of the left carotid artery was occlusive just before it entered the skull (Figs. 1 and 3). The arterial phase of the procedure also detected the absence of perfusion of the left middle cerebral artery and bad perfusion of both kidneys. Lack of opacification of both coronary arteries was clear during this phase (Fig. 2, A and B) but not uniform; there was total occlusion of the left branch and a small amount of contrast still visible in the right coronary lumen. No change appeared in coronary perfusion at the dynamic phase of the procedure. In contrary, better perfusion was then detectable in the renal and cerebral arteries. We interpreted our findings as a suspected mechanical obstruction of flow through the coronary ostia. A thrombus attached to the lumen of the abdominal aortic wall was visible, and tight vertebral artery stenoses were also seen. The venous phase brought no relevant contribution to the diagnosis.
Conventional Autopsy Conventional autopsy was performed the following day, around 68 hours after death and 20 hours after MPMCTA. Autopsy findings confirmed the dissection. Specifically, in the intimal flap, there was a visible tear of the first posterior portion of the aorta, just above the aortic root cusps, and bloody
FIGURE 1. Three-dimensional VR reformations of the aorta and its branches. A, Global view of the aorta and its branches. Arrows indicate malperfusion of the vessels. B, A closer view of the thoracic aorta and the cervicobrachial branches showing the dissection line in the ascending aorta (red arrows) and malperfusion of the right coronary artery (white arrow) and the left carotid artery (orange arrow). C, A closer view of the abdominal aorta showing the dissection line (red arrows), which is partially hidden by calcifications, and malperfusion of the right renal artery (orange arrow).
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Acute Aortic Dissection With Malperfusion
FIGURE 2. Axial images of the arterial phase of MPMCTA showing lack of perfusion of the left coronary artery (arrow in A), stenosis with opacification of the origin of the right coronary artery only (arrow in B), and prolongation of the dissection with malperfusion of the right renal artery (arrow in C).
infiltration of the aortic root. There was no pericardial effusion. Coronary arteries were not directly involved by the dissection itself. The dissection extended downward to the renal arteries, progressing upward through both carotid arteries (Fig. 3B and C). There was an ulcerated plaque of atherosclerosis with a bicolor thrombus attached to it under the renal ostia. Macroscopic evaluation revealed severe atherosclerosis involving the coronary arteries as well as the carotid bifurcations, right vertebral artery, and renal ostia. The stenoses were estimated to occlude at least 80% of the lumens of the right coronary artery and the left renal artery. The heart weighed 635 g, and there was major left and right ventricular hypertrophy. Tissue samples for histologic investigation were collected during the autopsy from the main organs, including brain tissue, as well as from several specific regions of the aorta and its branches according to standard procedures.
Histologic Analysis In addition to conventional histological techniques, that is, hematoxylin and eosin staining, Verhoeff-Van Gieson for elastic fibers (VGEL) staining was performed on samples from the vascular system. These analyses showed fresh aortic dissection with extension in the left carotid artery and right renal artery, confirming the diagnosis. Aortic root samples also showed partial involvement. Occlusion of the left carotid artery by the false lumen was obvious in the hematoxylin and eosin staining of transverse sections (Fig. 3D). Hematoxylin and eosin staining did not reveal any obvious myocardial damage.
Immunohistochemical Investigations To verify the eventual occurrence of ischemic cardiac damage from coronary occlusion, we performed immunohistochemical investigations using antibodies to the markers fibronectin, C5b-9, myoglobin, and troponin C to stain paraffin-embedded * 2014 Lippincott Williams & Wilkins
heart tissue samples.14,15 Use of the fibronectin antibody resulted in strongly stained disseminated cells, especially in the subendocardial regions of both ventricles. There was also positive staining within the myocardium wall that was more severe in the right ventricle (Fig. 4). Immunohistochemical staining using the antibodies against the terminal complement complex C5b-9, myoglobin, and troponin C was negative. These results supported a finding of hypoxic myocardium.
Toxicological Analyses We performed routine toxicological screening to exclude any possibility of acute intoxication. Comprehensive drug screening, including screening for illicit and licit drugs, was performed on blood samples and gastric contents using gas chromatographyY mass spectrometry and on blood by liquid chromatography with diode array detection. Blood samples were screened for volatile substances using headspace gas chromatographyYflame ionization detection. Although acute intoxication was discarded, several substances were observed in postmortem samples. A metabolite of metoprolol, a selective A1 receptor blocker that the victim was taking as part of his medical treatment, was detected in the blood. Low concentrations of 4 benzodiazepines were measured in blood by liquid chromatography coupled to tandem mass spectrometry, including diazepam (7 Kg/L), nordiazepam (G5 Kg/L), oxazepam (70 Kg/L), and lorazepam (8 Kg/L). Caffeine was detected in the blood and gastric samples.
Medicolegal Conclusions Death was attributed to malperfusion of the coronary and carotid arteries in the context of an acute aortic type A dissection.
DISCUSSION Among cardiovascular diseases, aortic dissection is a major natural cause of death with well-known etiology.16 Acute mortality www.amjforensicmedicine.com
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FIGURE 3. Multiphase postmortem CT angiography, autopsy, and histologic findings all showed malperfusion of the left carotid artery due to nearly complete occlusion by the false lumen. A, Axial image during the arterial phase of MPMCTA showing a typical semilunar image of dissection of the left carotid artery (arrow). B, Aorta and brachiocervical branches after formalin fixation show the dissection of the left coronary artery with the original lumen (black arrow) being compressed by the false lumen (red arrow). C, Transverse samples taken from the dissected left coronary artery for histologic analysis show massive occlusion of the original lumen, similar to what was seen on the radiologic image. D, Hematoxylin and eosin staining of 1 of the transverse samples shown in C. The original lumen corresponds to the semilunar opacification seen during the arterial phase of MPMCTA.
is principally due to complications of the dissection involving the ascending aorta. This involvement mainly induces cardiac tamponade and acute myocardial ischemia due to coronary occlusion, most commonly involving the right coronary artery. There are also potential neurologic problems due to extension of the dissection in the carotid arteries or due to reduction of carotid blood flow.17 One study reported that there was involvement of the major branches of the aorta in 41% of all aortic dissections in victims autopsied in clinical pathology.18 Stenoses of the coronary ostia were described in 4% of the cases. Another report on a series of 335 cases of spontaneous aortic dissection detected on patient arrival at a hospital found noncardiovascular complications involving aortic branches in 33% of the cases. There was a strong correlation between stroke and carotid occlusion, and the authors stated that death was specifically related to vascular occlusion, such as carotid, mesenteric, or renal artery involvement, when death was not immediately related to the aortic rupture.19 Another study of 339 patients who underwent surgical management of aortic dissection found similar results, with 30.7% of the cases involving aortic branch compression.20 Computed tomographic angiography is used routinely in clinical investigation of chest pain. It is considered the clinical reference standard in cases with a suspicion of acute aortic
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FIGURE 4. Immunohistochemical staining with an antifibronectin antibody. The myocardium shows positive staining, especially on the right posterior wall (original magnification 100). * 2014 Lippincott Williams & Wilkins
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syndrome. This technique allows the clinician to analyze which kind of obstruction process is involved, a static or a dynamic one. Static obstruction occurs when the intimal flap extends into the ostium of the branching vessel without a distal reentry point, resulting in increased pressure or thrombus formation in the false lumen within the branch vessel, causing focal stenosis and end-organ ischemia. Dynamic obstruction affects vessels arising from the true lumen, when the intimal flap spares the branching vessel but prolapses and covers the branch vessel ostium like a curtain.21,22 Thus, in the present case, the postmortem images are speaking about mechanical obstruction in both coronary ostia, with no flow in the left branch and partial proximal perfusion in the right one. At autopsy, no thrombus was described at the aortic root, with free coronary ostia. The dissection itself did not extend in the coronary arteries. Considering the information given by the MPMCTA together with the autopsy results, we suspect a dynamic obstruction of both coronary arteries, especially the left one. In our protocol, the contrast media follow a retrograde pathway,12 which leads us to caution in the interpretation of our images. Postmortem CT angiography has already proven its value in helping forensic investigators, especially by concerning the visualization of vascular findings.23Y25 Exploration of the vessels using CT angiography is accurate and faster than anatomical dissections, permitting to work on images, for example, by 3-dimensional VR programs, after release of the body. An approach by a consensus of radiologists and forensic examiners provides more reliable interpretation. Using the standardized MPMCTA protocol normally allows complete visualization of the entire arterial system. At our institute, we have performed approximately 350 examinations using this technique. To avoid misinterpretation of the angiographic images, a detailed study describing technique-related artifacts had been carried out recently.26 Although it is possible that a single vessel can be occluded by a postmortem clot, which can mimic an in vivo thrombus,24 most such artifacts disappear during the dynamic phase of angiography. In the case we present here, the nonopacification of the coronary arteries remained stable during all 3 phases, indicating that the images were not postmortem artifacts. In addition, none of the 350 cases examined in our institute have shown nonopacification of both coronary arteries, nor have any of the examined cases shown artifact-based occlusion of the cervical part of a carotid artery. For all these reasons, we concluded that the occlusion of the coronary arteries and the occlusion of the left carotid artery were not artifacts but were due to mechanical obstruction of the vascular lumen. Macroscopic dissections, performed carefully, can describe the dissection extension in great detail. When opening the vessel, it is possible to look at the precise localization of the intimal tear, which is classically located in the proximal segment of the ascending aorta, in the great curve close to the right coronary ostium, where tension forces are known to be high. However, this type of examination is time-consuming, especially as performed in the present case (Fig. 3), where we could find a posterior intimal tear. Conventional histologic investigations confirmed the aortic dissection, which was a classic tear at the junction of the external third and the internal two thirds of the media. Elastin staining made the aortic dissection obvious. Staining allowed us to evaluate the extent of the atherosclerotic illness and to estimate the lumen obstruction in several arteries. We graded the obstruction as a maximum of 80% obstruction of the right coronary artery and the left renal artery. Except for the severe arteriosclerosis, no other pathologic changes of the arterial walls were observed that could be interpreted as leading to aortic dissection. * 2014 Lippincott Williams & Wilkins
Acute Aortic Dissection With Malperfusion
The immunohistochemical staining did not confirm the hypothesis of myocardial ischemia after coronary obstruction. Fibronectin is an early marker of myocardial ischemia; however, it has low specificity because there can be positive fibronectin staining in cases of global hypoxia.27 Our findings might be attributable to an ischemic mechanism due to coronary obstruction that very rapidly led to malignant arrhythmia and death. However, carotid involvement with cerebral malperfusion must also be taken in consideration when determining the cause of death. In conclusion, this case illustrates the important contribution of MPMCTA in exploring the vascular system and shows how correlation of the imaging findings with histopathology results gives an even better understanding of the cause of death. This is the first case to be described in the literature that shows that postmortem CT angiography can not only visualize lesions in the vascular system but can also provide information about related changes in dynamic flow in the vascular system. ACKNOWLEDGMENTS The authors thank Dr Annelise Wohlwend, Geneva University, Switzerland, for helping them to obtain quality image of the left carotid artery.
REFERENCES 1. Jeffery AJ. The role of computed tomography in adult post-mortem examinations: an overview. Diagn Histopathol. 2010;16:546Y551. 2. O’Donnell C. An image of sudden death: utility of routine post-mortem computed tomography scanning in medico-legal autopsy practice. Diagn Histopathol. 2010;16:552Y555. 3. Weustink AC, Hunink MG, van Dijke CF, et al. Minimally invasive autopsy: an alternative to conventional autopsy? Radiology. 2009;3:897Y904. 4. Okuda T, Shiotani S, Sakamoto N, et al. Background and current status of postmortem imaging in Japan: short history of ‘‘Autopsy imaging (Ai)’’. Forensic Sci Int. 2013;225:3Y8. 5. Jackowski C, Sonnenschein M, Thali MJ, et al. Virtopsy: postmortem minimally invasive angiography using cross section techniquesVimplementation and preliminary results. J Forensic Sci. 2005;5:1175Y1186. 6. Grabherr S, Gygax E, Sollberger B, et al. Two-step postmortem angiography with a modified heart-lung machine: preliminary results. AJR Am J Roentgenol. 2008;2:345Y351. 7. Roberts IS, Benamore RE, Peebles C, et al. Technical report: diagnosis of coronary artery disease using minimally invasive autopsy: evaluation of a novel method of post-mortem coronary CT angiography. Clin Radiol. 2011;7:645Y650. 8. Brough AL, Rutty GN, Black S, et al. Post-mortem computed tomography and 3D imaging: anthropological applications for juvenile remains. Forensic Sci Med Pathol. 2012;8(3):270Y279. 9. Lizuka K, Sakamoto N, Kawasaki H, et al. Usefulness of contrast-enhanced postmortem CT. Innervision. 2009;24:89Y92. 10. Grabherr S, Djonov V, Yen K, et al. Postmortem angiography: review of former and current methods. AJR Am J Roentgenol. 2007;3:832Y838. 11. Grabherr S, Djonov V, Friess A, et al. Postmortem angiography after vascular perfusion with diesel oil and a lipophilic contrast agent. AJR Am J Roentgenol. 2006;5:515Y523. 12. Grabherr S, Doenz F, Steger B, et al. Multi-phase post-mortem CT angiography: development of a standardized protocol. Int J Legal Med. 2011;6:791Y802.
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13. Schneider B, Chevallier C, Dominguez A, et al. The forensic radiographer: a new member in the medicolegal team. Am J Forensic Med Pathol. 2012;1:30Y36.
20. Oderich GS, Panneton JM, Bower TC, et al. Aortic dissection with aortic side branch compromise: impact of malperfusion on patient outcome. Perspect Vasc Surg Endovasc Ther. 2008;2:190Y200.
14. Brinkmann B, Sepulchre MA, Fechner G. The application of selected histochemical and immunohistochemical markers and procedures to the diagnosis of early myocardial damage. Int J Legal Med. 1993;3:135Y141.
21. Blanke P, Apfaltrer P, Ebersberger U, et al. CT detection of pulmonary embolism and aortic dissection. Cardiol Clin. 2012;1:103Y116.
15. Ortmann C, Pfeiffer H, Brinkmann B. A comparative study on the immunohistochemical detection of early myocardial damage. Int J Legal Med. 2000;4:215Y220. 16. Nienaber CA, Eagle KA. Aortic dissection: new frontiers in diagnosis and management: Part I: from etiology to diagnostic strategies. Circulation. 2003;5:628Y635. 17. Manning WJ. Clinical manifestations and diagnosis of aortic dissection. [UpToDate Web site]. October 25, 2012. Available at: http://www.uptodate.com. 2013 UpToDate, Inc. Accessed May 15, 2013. 18. Me´sza´ros I, Mo´rocz J, Szla´vi J, et al. Epidemiology and clinicopathology of aortic dissection. Chest. 2000;5:1271Y1278. 19. Cambria RP, Brewster DC, Gertler J, et al. Vascular complications associated with spontaneous aortic dissection. J Vasc Surg. 1988;2:199Y209.
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22. Williams DM, Lee DY, Hamilton BH, et al. The dissected aorta: part III. Anatomy and radiologic diagnosis of branch-vessel compromise. Radiology. 1997;203(1):37Y44. 23. Saunders S, Morgan B, Raj V, et al. Targeted post-mortem computed tomography cardiac angiography: proof of concept. Int J Legal Med. 2011;4:609Y616. 24. Michaud K, Grabherr S, Doenz F, et al. Evaluation of postmortem MDCT and MDCT-angiography for the investigation of sudden cardiac death related to atherosclerotic coronary artery disease. Int J Cardiovasc Imaging. 2012;28(7):1807Y1822. 25. Chevallier C, Doenz F, Vaucher P, et al. Postmortem computed tomography angiography vs. conventional autopsy: advantages and inconveniences of each method. Int J Legal Med. 2013;127(5):981Y989. 26. Bruguier C, Mosimann PJ, Vaucher P, et al. Multi-phase postmortem CT angiography: recognizing technique-related artefacts and pitfalls. Int J Legal Med. 2013;127(3):639Y652. 27. Bajanowski T, Ortmann C, Teige K, et al. Pathological changes of the heart in sudden infant death. Int J Legal Med. 2003;4:193Y302.
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Acute Aortic Dissection With Carotid and Coronary Malperfusion From Imaging to Pathology Christelle Lardi, MD,* Johannes-Alexander Lobrinus, MD,Þ Francesco Doenz, MD,þ Tony Fracasso, MD, PD,* Marc Augsburger, PhD,*§ Patrice Mangin, MD, PhD,*§ and Silke Grabherr, MD, PD§ Abstract: Postmortem imaging, including postmortem computed tomography angiography, has become an integral tool in forensic investigation in recent years. A relatively new technique, multiphase postmortem computed tomography angiography, allows detailed visualization of the vascular system and makes it possible to evaluate the dynamic perfusion of aortic branches, including the coronary arteries. Here, we report a case of aortic dissection involving the ascending aorta (type A) with coronary and carotid malperfusion. This case illustrates the complementary use of many of the diagnostic tools that are now available in forensic practice, from imaging to conventional autopsy to pathologic techniques such as immunohistochemistry. Key Words: forensic imaging, postmortem angiography, aortic dissection, malperfusion
forensic radiographers.13 The combination of postmortem imaging and conventional autopsy can even be considered to be the new criterion standard for forensic investigation.1 Here, we present a case that illustrates how many of the diagnostic tools that are now available in forensic practice could be complementarily used to establish the cause of death. We present a case of an acute aortic type A dissection, according to the Stanford classification, and show how imaging and autopsy, used together, revealed the extent of the dissection in several aortic branches. We also show that only postmortem angiography could detect a dynamic complication that led to death in a case of coronary malperfusion generated by the dissection of the aortic wall. We also investigated the use of immunohistochemistry to evaluate early ischemic myocardium injury.
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n the past decade, forensic research teams all over the world have begun to use postmortem imaging in their analyses.1Y4 Especially in Switzerland,5,6 England,7,8 and Japan,4,9 such teams have worked to develop postmortem computed tomography (CT) angiography techniques. Postmortem CT angiography5,10,11 is a minimally invasive approach that allows very accurate and detailed investigation of the vascular system and thus helps the forensic team to detect vascular lesions. Using a standardized protocol developed recently, very high quality postmortem CT angiographies of the whole body can be performed in 1 hour.12 Multiphase postmortem CT angiography (MPMCTA) includes 1 native CT scan plus 3 angiographic phases (ie, arterial, venous, and dynamic phases). Using MPMCTA, we will discuss the possibility of detecting dynamic perfusion problems that are invisible using only native CT. At the University Center for Legal Medicine in Lausanne, Switzerland, MPMCTA is performed before classic autopsy as part of the routine investigation of cases in which there is a suspicion of vascular lesions. The images are then correlated with conventional autopsy findings. Both the standardized protocol and the entire radiologic examination can be carried out by Manuscript received October 2, 2013; accepted December 1, 2013. From the *University Center of Legal Medicine Lausanne-Geneva, Geneva University Hospitals; †Department of Pathology, Geneva University Hospitals, Geneva; ‡Department of Diagnostic and Interventional Radiology, University Hospital of Lausanne; and §University Center of Legal Medicine Lausanne-Geneva, University Hospital of Lausanne, Lausanne, Switzerland. This study was funded by the Promotion Agency for Innovation of the Swiss Confederation (KTI Nr.10221.1 PFIW-IW) and by the Fondation Leenaards, Lausanne, Switzerland. The authors report no conflicts of interest. Reprints: Christelle Lardi, MD, University Center of Legal Medicine Lausanne-Geneva, Geneva University Hospitals, Michel-Servet 1, CH-2011 Geneva 4, Switzerland. E-mail: [email protected]. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0195-7910/14/3503Y0157 DOI: 10.1097/PAF.0000000000000098
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CASE REPORT We report the case of a 61-year-old man who was found dead in his bed by his wife 1 morning. The emergency staff called to the site confirmed his death and did not initiate resuscitation measures. The victim had received regular medical checkups after undergoing liver transplantation 10 years before. He also had known general cardiovascular problems (hypertension and stroke) as well as chronic renal insufficiency.
Native CT Scan Before any manipulation of the corpse, a native CT scan was carried out around 46 hours since death using an 8-row CT unit (CT LightSpeed 8; GE Healthcare, Milwaukee, Wis) using the following scan parameters: field of view (FOV), 50 cm; slice thickness, 2.5 mm; interval of reconstruction, 2 mm, 1 mm; 120 kilovolt (peak) kV(p); 280 mA, 300 mA; and noise index, 15. The images obtained using native CT were viewed immediately by a forensic pathologist who was experienced in forensic imaging. They revealed the presence of extended vascular calcification and a flap of the vascular wall in the aortic arch. There was thus a suspicion of an aortic dissection, and the forensic pathologist in charge of the case decided to perform an MPMCTA. This examination was immediately carried out during the following hour.
External Examination The external examination, which was performed by the forensic pathologist in charge of the case, did not reveal any major traumatic lesions. There were several bruises of different ages on his back, thorax, and limbs, as well as some puncture/ injection sites related to the man’s recent hospitalization. The man was slightly overweight, with a body mass index of 26 (weight, 73 kg; height, 167 cm).
Collection of Postmortem Liquid Samples Samples for toxicological analyses, that is, peripheral and cardiac blood, urine, vitreous humor, and cerebrospinal fluid, were www.amjforensicmedicine.com
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collected under CT guidance (for urine and cardiac blood) by a forensic radiographer as described by Schneider et al.13 Urine was collected in a glucose urine tube. Vitreous humor and cerebrospinal fluid were sampled in a neutral serum tube and a glucose tube for postmortem biochemistry. Other fluids such as gastric contents and pericardial fluid were collected during conventional autopsy.
Multiphase Postmortem CT Angiography According to the standardized protocol described by Grabherr et al,12 cannulation of the femoral vessels was performed on 1 side using cannulas with a diameter of 16F for arteries and 18F for veins (MAQUET Gmbh & Co. KG, Rastatt, Germany). During the cannulation process, blood samples were collected in different tubes for toxicological and biochemical analysis. A recently developed pressure-controlled perfusion device (Virtangio; Fumedica AG) was used to inject a mixture of iodated contrast agent (6% of Angiofil; Fumedica AG, Switzerland) with paraffin oil (paraffinum liquidum, obtained from the local pharmacy). The arterial phase of MPMCTA was carried out using the following scan parameters: FOV, 50 cm; reconstructed slice thickness, 1.25 mm; reconstruction interval, 0.6 mm; 120 kV(p); and 280 mA. Scan parameters for the venous and dynamic phase were as follows: FOV, 50 cm; reconstructed slice thickness, 2.5 mm; reconstruction interval, 1.2 mm; 120 kV(p); and 280 mA.
Radiologic Interpretation All images were interpreted in a consensus reading by 2 board-certified radiologists (1 specialized in vascular radiology and 1 specialized in neuroradiology) and by 1 board-certified forensic pathologist who was trained in forensic imaging. A postmortem radiologic report was prepared that described all findings from native CT and from each phase of the MPMCTA.
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Three-dimensional volume-rendered (VR) images were only used for better visualization of the present communication. The native CT scan mainly showed severe calcification of the aorta and its major branches. The 3 coronary arteries and the aortic valve were particularly involved. An aortic dissection of both ascending and descending part of the aorta was suspected. Multiphase postmortem CT angiography could then confirm the diagnosis and demonstrate the presence of an aortic wall dissection that started from the ascending aorta and progressed to the abdominal aorta and which included both carotid arteries as well as the right renal artery (Figs. 1 and 2). Dissection of the left carotid artery was occlusive just before it entered the skull (Figs. 1 and 3). The arterial phase of the procedure also detected the absence of perfusion of the left middle cerebral artery and bad perfusion of both kidneys. Lack of opacification of both coronary arteries was clear during this phase (Fig. 2, A and B) but not uniform; there was total occlusion of the left branch and a small amount of contrast still visible in the right coronary lumen. No change appeared in coronary perfusion at the dynamic phase of the procedure. In contrary, better perfusion was then detectable in the renal and cerebral arteries. We interpreted our findings as a suspected mechanical obstruction of flow through the coronary ostia. A thrombus attached to the lumen of the abdominal aortic wall was visible, and tight vertebral artery stenoses were also seen. The venous phase brought no relevant contribution to the diagnosis.
Conventional Autopsy Conventional autopsy was performed the following day, around 68 hours after death and 20 hours after MPMCTA. Autopsy findings confirmed the dissection. Specifically, in the intimal flap, there was a visible tear of the first posterior portion of the aorta, just above the aortic root cusps, and bloody
FIGURE 1. Three-dimensional VR reformations of the aorta and its branches. A, Global view of the aorta and its branches. Arrows indicate malperfusion of the vessels. B, A closer view of the thoracic aorta and the cervicobrachial branches showing the dissection line in the ascending aorta (red arrows) and malperfusion of the right coronary artery (white arrow) and the left carotid artery (orange arrow). C, A closer view of the abdominal aorta showing the dissection line (red arrows), which is partially hidden by calcifications, and malperfusion of the right renal artery (orange arrow).
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Acute Aortic Dissection With Malperfusion
FIGURE 2. Axial images of the arterial phase of MPMCTA showing lack of perfusion of the left coronary artery (arrow in A), stenosis with opacification of the origin of the right coronary artery only (arrow in B), and prolongation of the dissection with malperfusion of the right renal artery (arrow in C).
infiltration of the aortic root. There was no pericardial effusion. Coronary arteries were not directly involved by the dissection itself. The dissection extended downward to the renal arteries, progressing upward through both carotid arteries (Fig. 3B and C). There was an ulcerated plaque of atherosclerosis with a bicolor thrombus attached to it under the renal ostia. Macroscopic evaluation revealed severe atherosclerosis involving the coronary arteries as well as the carotid bifurcations, right vertebral artery, and renal ostia. The stenoses were estimated to occlude at least 80% of the lumens of the right coronary artery and the left renal artery. The heart weighed 635 g, and there was major left and right ventricular hypertrophy. Tissue samples for histologic investigation were collected during the autopsy from the main organs, including brain tissue, as well as from several specific regions of the aorta and its branches according to standard procedures.
Histologic Analysis In addition to conventional histological techniques, that is, hematoxylin and eosin staining, Verhoeff-Van Gieson for elastic fibers (VGEL) staining was performed on samples from the vascular system. These analyses showed fresh aortic dissection with extension in the left carotid artery and right renal artery, confirming the diagnosis. Aortic root samples also showed partial involvement. Occlusion of the left carotid artery by the false lumen was obvious in the hematoxylin and eosin staining of transverse sections (Fig. 3D). Hematoxylin and eosin staining did not reveal any obvious myocardial damage.
Immunohistochemical Investigations To verify the eventual occurrence of ischemic cardiac damage from coronary occlusion, we performed immunohistochemical investigations using antibodies to the markers fibronectin, C5b-9, myoglobin, and troponin C to stain paraffin-embedded * 2014 Lippincott Williams & Wilkins
heart tissue samples.14,15 Use of the fibronectin antibody resulted in strongly stained disseminated cells, especially in the subendocardial regions of both ventricles. There was also positive staining within the myocardium wall that was more severe in the right ventricle (Fig. 4). Immunohistochemical staining using the antibodies against the terminal complement complex C5b-9, myoglobin, and troponin C was negative. These results supported a finding of hypoxic myocardium.
Toxicological Analyses We performed routine toxicological screening to exclude any possibility of acute intoxication. Comprehensive drug screening, including screening for illicit and licit drugs, was performed on blood samples and gastric contents using gas chromatographyY mass spectrometry and on blood by liquid chromatography with diode array detection. Blood samples were screened for volatile substances using headspace gas chromatographyYflame ionization detection. Although acute intoxication was discarded, several substances were observed in postmortem samples. A metabolite of metoprolol, a selective A1 receptor blocker that the victim was taking as part of his medical treatment, was detected in the blood. Low concentrations of 4 benzodiazepines were measured in blood by liquid chromatography coupled to tandem mass spectrometry, including diazepam (7 Kg/L), nordiazepam (G5 Kg/L), oxazepam (70 Kg/L), and lorazepam (8 Kg/L). Caffeine was detected in the blood and gastric samples.
Medicolegal Conclusions Death was attributed to malperfusion of the coronary and carotid arteries in the context of an acute aortic type A dissection.
DISCUSSION Among cardiovascular diseases, aortic dissection is a major natural cause of death with well-known etiology.16 Acute mortality www.amjforensicmedicine.com
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FIGURE 3. Multiphase postmortem CT angiography, autopsy, and histologic findings all showed malperfusion of the left carotid artery due to nearly complete occlusion by the false lumen. A, Axial image during the arterial phase of MPMCTA showing a typical semilunar image of dissection of the left carotid artery (arrow). B, Aorta and brachiocervical branches after formalin fixation show the dissection of the left coronary artery with the original lumen (black arrow) being compressed by the false lumen (red arrow). C, Transverse samples taken from the dissected left coronary artery for histologic analysis show massive occlusion of the original lumen, similar to what was seen on the radiologic image. D, Hematoxylin and eosin staining of 1 of the transverse samples shown in C. The original lumen corresponds to the semilunar opacification seen during the arterial phase of MPMCTA.
is principally due to complications of the dissection involving the ascending aorta. This involvement mainly induces cardiac tamponade and acute myocardial ischemia due to coronary occlusion, most commonly involving the right coronary artery. There are also potential neurologic problems due to extension of the dissection in the carotid arteries or due to reduction of carotid blood flow.17 One study reported that there was involvement of the major branches of the aorta in 41% of all aortic dissections in victims autopsied in clinical pathology.18 Stenoses of the coronary ostia were described in 4% of the cases. Another report on a series of 335 cases of spontaneous aortic dissection detected on patient arrival at a hospital found noncardiovascular complications involving aortic branches in 33% of the cases. There was a strong correlation between stroke and carotid occlusion, and the authors stated that death was specifically related to vascular occlusion, such as carotid, mesenteric, or renal artery involvement, when death was not immediately related to the aortic rupture.19 Another study of 339 patients who underwent surgical management of aortic dissection found similar results, with 30.7% of the cases involving aortic branch compression.20 Computed tomographic angiography is used routinely in clinical investigation of chest pain. It is considered the clinical reference standard in cases with a suspicion of acute aortic
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FIGURE 4. Immunohistochemical staining with an antifibronectin antibody. The myocardium shows positive staining, especially on the right posterior wall (original magnification 100). * 2014 Lippincott Williams & Wilkins
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syndrome. This technique allows the clinician to analyze which kind of obstruction process is involved, a static or a dynamic one. Static obstruction occurs when the intimal flap extends into the ostium of the branching vessel without a distal reentry point, resulting in increased pressure or thrombus formation in the false lumen within the branch vessel, causing focal stenosis and end-organ ischemia. Dynamic obstruction affects vessels arising from the true lumen, when the intimal flap spares the branching vessel but prolapses and covers the branch vessel ostium like a curtain.21,22 Thus, in the present case, the postmortem images are speaking about mechanical obstruction in both coronary ostia, with no flow in the left branch and partial proximal perfusion in the right one. At autopsy, no thrombus was described at the aortic root, with free coronary ostia. The dissection itself did not extend in the coronary arteries. Considering the information given by the MPMCTA together with the autopsy results, we suspect a dynamic obstruction of both coronary arteries, especially the left one. In our protocol, the contrast media follow a retrograde pathway,12 which leads us to caution in the interpretation of our images. Postmortem CT angiography has already proven its value in helping forensic investigators, especially by concerning the visualization of vascular findings.23Y25 Exploration of the vessels using CT angiography is accurate and faster than anatomical dissections, permitting to work on images, for example, by 3-dimensional VR programs, after release of the body. An approach by a consensus of radiologists and forensic examiners provides more reliable interpretation. Using the standardized MPMCTA protocol normally allows complete visualization of the entire arterial system. At our institute, we have performed approximately 350 examinations using this technique. To avoid misinterpretation of the angiographic images, a detailed study describing technique-related artifacts had been carried out recently.26 Although it is possible that a single vessel can be occluded by a postmortem clot, which can mimic an in vivo thrombus,24 most such artifacts disappear during the dynamic phase of angiography. In the case we present here, the nonopacification of the coronary arteries remained stable during all 3 phases, indicating that the images were not postmortem artifacts. In addition, none of the 350 cases examined in our institute have shown nonopacification of both coronary arteries, nor have any of the examined cases shown artifact-based occlusion of the cervical part of a carotid artery. For all these reasons, we concluded that the occlusion of the coronary arteries and the occlusion of the left carotid artery were not artifacts but were due to mechanical obstruction of the vascular lumen. Macroscopic dissections, performed carefully, can describe the dissection extension in great detail. When opening the vessel, it is possible to look at the precise localization of the intimal tear, which is classically located in the proximal segment of the ascending aorta, in the great curve close to the right coronary ostium, where tension forces are known to be high. However, this type of examination is time-consuming, especially as performed in the present case (Fig. 3), where we could find a posterior intimal tear. Conventional histologic investigations confirmed the aortic dissection, which was a classic tear at the junction of the external third and the internal two thirds of the media. Elastin staining made the aortic dissection obvious. Staining allowed us to evaluate the extent of the atherosclerotic illness and to estimate the lumen obstruction in several arteries. We graded the obstruction as a maximum of 80% obstruction of the right coronary artery and the left renal artery. Except for the severe arteriosclerosis, no other pathologic changes of the arterial walls were observed that could be interpreted as leading to aortic dissection. * 2014 Lippincott Williams & Wilkins
Acute Aortic Dissection With Malperfusion
The immunohistochemical staining did not confirm the hypothesis of myocardial ischemia after coronary obstruction. Fibronectin is an early marker of myocardial ischemia; however, it has low specificity because there can be positive fibronectin staining in cases of global hypoxia.27 Our findings might be attributable to an ischemic mechanism due to coronary obstruction that very rapidly led to malignant arrhythmia and death. However, carotid involvement with cerebral malperfusion must also be taken in consideration when determining the cause of death. In conclusion, this case illustrates the important contribution of MPMCTA in exploring the vascular system and shows how correlation of the imaging findings with histopathology results gives an even better understanding of the cause of death. This is the first case to be described in the literature that shows that postmortem CT angiography can not only visualize lesions in the vascular system but can also provide information about related changes in dynamic flow in the vascular system. ACKNOWLEDGMENTS The authors thank Dr Annelise Wohlwend, Geneva University, Switzerland, for helping them to obtain quality image of the left carotid artery.
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