Usefulness of fat attenuation index in postmortem CT for identifying responsible vessels in acute coronary syndromes: A case report.

Postmortem imaging, particularly unenhanced postmortem computed tomography (PMCT), has been increasingly utilized for pathological or judicial examination as a substitute for conventional autopsy, to compensate very low autopsy rates. While unenhanced PMCT has a limitation in diagnosing acute coronary syndromes, the fat attenuation index (FAI) which is a novel imaging biomarker measured by clinical coronary CT angiography (CCTA), has been known to noninvasively detect coronary artery inflammation. We investigated the postmortem diagnostic usefulness of perivascular FAI measured by CCTA in a 61-year-old male who died suddenly after chest pain. PMCT and autopsy were conducted 92 hours after death. FAI measurement results were -57 Hounsfield units (HU) in the right coronary artery (RCA), -73 HU in the left anterior descending artery (LAD), and -64 HU in the left circumflex artery (LCX). Autopsy revealed significant stenosis in the RCA and LCX, but no significant stenosis was found in the LAD. The elevated FAI in the RCA suggested acute inflammation, which agreed with the autopsy findings. This case is the first to demonstrate effectiveness of FAI measured with PMCT for identifying the vessels responsible for acute coronary syndromes, indicating its potential in postmortem diagnosis.

Postmortem computed tomography findings as evidence of traffic accident-related fatal injury.

PURPOSE: Most traumatic deaths in Japan are due to nonpenetrating injuries, especially those that result from traffic accidents; however, the autopsy rate of traffic accident-related deaths is only about 5%. We investigated the diagnostic ability of postmortem computed tomography (PMCT) in cases of fatal trauma after traffic accidents. MATERIALS AND METHODS: Our subjects were 78 subjects (59 males, 19 females; mean age 50 years, range 15-87 years) who were brought to our institution in cardiopulmonary arrest on arrival after traffic accidents and died despite resuscitation attempts. PMCT findings of damage to the head, neck, thorax, abdomen, and pelvis were classified into three grades according to the Abbreviated Injury Scale (AIS) severity: A: 1 (minor), 2 (moderate); B: 3 (serious), 4 (severe), 5 (critical); C: 6 (maximum). RESULTS: The percentage ratio of A/B/C in 78 head injuries was 32/60/8, in 41 neck injuries 83/5/12, in 76 thorax injuries 5/38/57, in 76 abdominal injuries 70/24/7, and in 76 pelvic injuries 79/21/0, respectively. CONCLUSION: PMCT can detect or presume fatal trauma when diagnosing the cause of death after traffic accidents.

Presence of beta-linked GalNAc residues on N-glycans of human thyroglobulin.

Hepatic asialoglycoprotein receptor, which may mediate the clearance of circulating thyroglobulin, is known to have a high affinity for GalNAc. Recently, the receptor has been reported to be present also in the thyroid, implicating interaction with thyroglobulin. Here, mammalian thyroglobulins were analyzed for GalNAc termini by Western blotting with GalNAc-recognizing lectins labeled with peroxidase or (125)I. Wistaria floribunda lectin was found to bind human thyroglobulin and, to some extent, bovine, but not porcine thyroglobulin. After desialylation, the lectin bound all of the thyroglobulins tested. The binding was inhibited by competitive inhibitor GalNAc. Peptide N-glycanase treatment of human desialylated thyroglobulin resulted in the complete loss of reactivity with W. floribunda lectin, indicating that the binding sites are exclusively on N-glycans. The binding sites on human desialylated thyroglobulin were partly sensitive to beta-galactosidase, and the remainder was essentially sensitive to beta-N-acetylhexosaminidase. On the other hand, the binding sites of bovine and porcine desialylated thyroglobulins were totally sensitive to beta-galactosidase. Thus the lectin binds beta-Gal termini, as well as beta-GalNAc. GalNAc-specific Dolichos biflorus lectin also bound human thyroglobulin weakly. In contrast to W. floribunda lectin, desialylation diminished binding, suggesting that these two lectins recognize different GalNAc-terminated structures. Again, the binding was inhibited by GalNAc and by treatment with peptide N-glycanase. These results strongly indicate the presence of distinct GalNAc termini of N-glycans on human thyroglobulin.

Hepatic Relaxation Times from Postmortem MR Imaging of Adult Humans.

PURPOSE: To measure T1 and T2 values of hepatic postmortem magnetic resonance (PMMR) imaging. MATERIALS AND METHODS: We performed hepatic PMMR imaging of 22 deceased adults (16 men, 6 women; mean age, 56.3 years) whose deaths were for reasons other than liver injury or disease at a mean of 27.7 hours after death. Before imaging, the bodies were kept in cold storage at 4°C (mean rectal temperature, 17.6°C). We measured T1 and T2 values in the liver at two sites (the anterior segment of the right lobe and the lateral segment of the left lobe). We also investigated the influence of the body temperature and postmortem interval on T1 and T2 values. RESULTS: In the anterior segment of the right lobe and the lateral segment of the left lobe, T1 values of PMMR imaging were 524 ± 112 ms and 472 ± 104 ms (mean ± standard deviation), respectively; while T2 values were 42 ± 6 ms and 43 ± 8 ms, respectively. T1 and T2 values did not differ significantly between the two sites (P ≧ 0.05). Regarding temperature, the T2 values of hepatic PMMR imaging were linearly correlated with the body temperature, but the T1 values were not. The T1 and T2 values of the two sites in the liver did not correlate with the postmortem interval. CONCLUSION: Reduction in body temperature after death is considered to induce T1 and T2 value changes in the liver on PMMR imaging.

Effects of long-term administrations of aconitine on electrocardiogram and tissue concentrations of aconitine and its metabolites in mice.

Aconitum alkaloids are well known for their acute and high toxicity, for example, in the causation of severe arrhythmias leading to death. Aconitine, one of the major Aconitum alkaloids, is a highly toxic compound from the Aconitum species. However, there has been no studies reported on the influence of the chronic administration of aconitine. Thus, this study was conducted to investigate the influence of chronic administration of aconitine in experimental animal models. A dose of 1mg/kg per day was administered to the experimental animal models. We determined the concentration of aconitine and its metabolites (benzoylaconine and aconine) in organs and blood with gas chromatography/selected ion monitoring (GC/SIM). In addition, we concurrently recorded the electrocardiogram (ECG). Fifteen minutes after administration on day 0, the early aconitine administered group (acute group) revealed peak organ and blood concentration levels of aconitine with a gradual decrease, thereafter. The concentration of aconitine in organs and blood (from days 0 to 22; 90 min after the last administration of aconitine) gradually decreased according to repeated administration, whereas benzoylaconine and aconine increased. ECG revealed various types of arrhythmias. However, the frequency of arrhythmias remarkably decreased with time and repeated administration of aconitine. These results indicate two possibilities. First, the increase in the activity of aconitine metabolism. Secondly, the decrease of effectiveness to the heart due to long-term (chronic) administration of aconitine.

Pseudo-Hirschsprung's disease with rectal hypoganglionosis: an autopsied case of circulatory failure due to severe constipation.

We report a 21-year-old female patient who suddenly died of circulatory failure due to pressure from megacolon allied with pseudo-Hirschsprung's disease. Since 3 years before her death, she had exhibited the feeling of abdominal distention, which was diagnosed as constipation. However, her constipation did not respond well to the prescribed oral administration of laxatives and enemas. She was found dead at home in the morning, lying on her back. An autopsy revealed a decreased number of ganglion cells in the rectum, suggesting hypoganglionosis. In cases of intractable chronic constipation, careful investigation of the cause of such symptoms is important.

Possibility of visualization of gastrothorax based on unenhanced postmortem computed tomography/PMCT.

We present a fatal case of a gastrothorax due to an acute gastric volvulus resulting from a Bochdalek hernia. A 5-year-old boy without previous medical history was brought to our institution in a state of cardiopulmonary arrest and was subsequently pronounced dead. Postmortem computed tomography (PMCT) of the torso showed abdominal organs involving the lower section of the esophagus up to the entire stomach, the left side of the transverse colon, the entire spleen, and the tail of the pancreas herniated into the left thoracic cavity. The stomach was markedly expanded and a mesentero-axial (rotation along the short axis) volvulus was observed, displacing mediastinal structures to the right side and depressing the diaphragmatic contour. A PMCT of the thorax at the lung window setting revealed displacement of bilateral lungs. The bilateral lungs were severely atelectatic and congested. The PMCT findings mentioned above were consistent with the autopsy findings. PMCT can provide useful information for the diagnosis in cases we initially cannot predict any significant changes, for example, organ displacement.

Pericardial tear as a consequence of cardiopulmonary resuscitation (CPR) involving chest compression: a report of two postmortem cases of acute type A aortic dissection with hemopericardium.

We present two cases of a pericardial tear as a consequence of cardiopulmonary resuscitation involving chest compressions in fatal acute type A aortic dissection (AoD) with hemopericardium. For each case, postmortem computed tomography revealed a hematoma in the false lumen of the ascending aorta with a slight hemopericardium and a large left hemothorax, as well as focal pericardial dimpling and discontinuity around the left ventricle. At autopsy, we confirmed a convex lens-shape gaping pericardial tear at the left posterolateral site of the pericardium and a massive volume of bloody fluid in the left thoracic cavity. It has been hypothesized that the pericardium ruptured due to chest compressions during resuscitation in these cases of acute type A AoD with hemopericardium and that intrapericardial blood leakage through the pericardial tear resulted in a hemothorax.

Cerebral relaxation times from postmortem MR imaging of adults.

PURPOSE: We measured T1 and T2 values of cerebral postmortem magnetic resonance (PMMR) imaging and compared the data of cadavers with that of living human subjects. MATERIALS AND METHODS: We performed PMMR imaging of the brains of 30 adults (22 men, 8 women; mean age, 58.2 years) whose deaths were for reasons other than brain injury or disease at a mean of 29.4 hours after death. Before imaging, the bodies were kept in cold storage at 4°C (mean rectal temperature, 15.6°C). We measured T1 and T2 values in the brain bilaterally at 5 sites (bilateral caudate nucleus, putamen, thalamus and gray matter and white matter of the frontal lobe) and compared the data of PMMR imaging with that from MR imaging of the corresponding sites in 24 healthy volunteers (9 men, 15 women; mean age, 51.8 years). We also investigated the influence of body temperature on T1 and T2 values. RESULTS: Compared with MR imaging findings in the living subjects, PMMR imaging showed significantly shorter T1 values in the caudate nucleus, putamen, thalamus and gray matter and white matter of the frontal lobe and significantly longer T2 values in the gray matter and white matter of the frontal lobe; T2 values in the caudate nucleus, putamen, and thalamus showed no such differences. T1 values correlated significantly with body temperature in all 5 brain sites measured, but T2 values did not. CONCLUSION: Compared with findings of cerebral MR imaging in living adult subjects, those of PMMR imaging tended to demonstrate shorter T1 values and longer T2 values. We attribute this to increased water content of tissue, reduced pH, and reduced body temperature after death.

Can ruptured abdominal aortic aneurysm be accurately diagnosed as the cause of death without postmortem computed tomography when autopsies cannot be performed?

PURPOSE: This study aimed to conduct a multicentre retrospective review of cases to clarify how many ruptured abdominal aortic aneurysms (RAAAs) as the cause of death could be diagnosed without post-mortem computed tomography (PMCT) when autopsies cannot be performed. METHODS: We collected consecutive PMCT data from January 2002 to December 2009 from three institutes where PMCT examinations are performed on a routine basis for deceased patients with unknown causes of death. A total of 19 cases were identified where PMCT revealed RAAAs. Ante-mortem clinical presentations, post-mortem external examinations, and peri-mortem ultrasonography findings were assessed for their diagnostic accuracy. RESULTS: The correct diagnosis based on the classic triad of shock, acute abdominal pain, and pulsatile abdominal mass was made in only one of 19 (5.3%) patients. Shock, acute abdominal pain, and abdominal swelling were found in five of 19 (26%) patients. Shock and acute abdominal pain or abdominal swelling were found in two of 19 (10%) patients. Ten of 19 (53%) patients only had shock. Peri-mortem ultrasonography was performed in seven of 19 patients; one was diagnosed with RAAA (14%). No patients had pre-mortem CT examinations. CONCLUSIONS: Post-mortem diagnosis of RAAA is difficult to make based on ante-mortem clinical presentation, post-mortem external examinations, or peri-mortem ultrasonography. PMCT is recommended for diagnosing RAAA as the cause of death if pre-mortem CT examinations are not carried out when autopsies cannot be performed.

Optimization of Inversion Time for Postmortem Fluid-attenuated Inversion Recovery (FLAIR) MR Imaging at 1.5T: Temperature-based Suppression of Cerebrospinal Fluid.

PURPOSE: Signal intensity (SI) and image contrast on postmortem magnetic resonance (MR) imaging are different from those of imaging of living bodies. We sought to suppress the SI of cerebrospinal fluid (CSF) sufficiently for fluid-attenuated inversion recovery (FLAIR) sequence in postmortem MR (PMMR) imaging by optimizing inversion time (TI). MATERIALS AND METHODS: We subject 28 deceased patients to PMMR imaging 3 to 113 hours after confirmation of death (mean, 27.4 hrs.). PMMR imaging was performed at 1.5 tesla, and T1 values of CSF were measured with maps of relaxation time. Rectal temperatures (RT) measured immediately after PMMR imaging ranged from 6 to 32°C (mean, 15.4°C). We analyzed the relationship between T1 and RT statistically using Pearson's correlation coefficient. We obtained FLAIR images from one cadaver using both a TI routinely used for living bodies and an optimized TI calculated from the RT. RESULTS: T1 values of CSF ranged from 2159 to 4063 ms (mean 2962.4), and there was a significantly positive correlation between T1 and RT (r = 0.96, P < 0.0001). The regression expression for the relationship was T1 = 74.4 * RT + 1813 for a magnetic field strength of 1.5T. The SI of CSF was effectively suppressed with the optimized TI (0.693 * T1), namely, TI = 0.693 * (77.4 * RT + 1813). CONCLUSION: Use of the TI calculated from the linear regression of the T1 and RT optimizes the FLAIR sequence of PMMR imaging.

Sensitive determination of tetrodotoxin using column-switching liquid chromatography-mass spectrometry with electrospray ionization in mouse serum.

A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method coupled with a column-switching technique was developed for the determination of tetrodotoxin (TTX) in serum. An on-column, column-switching technique was employed to analyze TTX without pretreatment of the serum. The combination of a multimode column with reversed phases and cation exchange for TTX provided successful separation and MS determination in the ESI-positive mode. A 100-microL serum sample was injected directly into a precolumn. For TTX monitored at m/z 320.1 in the selective ion monitoring mode, the calibration curve was linear within the range 0.1-100 ng/mL, and the limit of detection was 0.5 ng/mL. Recoveries were around 90% for TTX. The present method allows successful analysis of TTX in serum. In conclusion, this new method is simple, accurate, and useful for the determination of TTX and should be of benefit to both forensic and clinical toxicology.

A column-switching LC/MS/ESI method for detecting tetrodotoxin and Aconitum alkaloids in serum.

A liquid chromatography-mass spectrometry-electrospray ionization (LC/MS/ESI) method coupled with a column-switching technique has been developed for the determination of tetrodotoxin (TTX) and Aconitum alkaloids and their metabolites, such as aconitine, mesaconitine, hypaconitine, jesaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconine and 14-anisoylaconine, in serum. An on-column column-switching technique was employed to analyze TTX and Aconitum alkaloids and their metabolites without pretreatment of the serum. Combination of a multimode column with reversed phases and cation exchange for TTX, and use of a multimode column with reversed phases and a hydrophobic polymer column for Aconitum alkaloids and their metabolites provided successful separation and MS determination in ESI positive mode. A 100 microl serum sample was directly injected into a precolumn. For TTX monitored at m/z 320.1 in the selected ion monitoring mode, the calibration curve was linear within the range 0.1-100 ng/ml and the limit of detection was 0.1 ng/ml. For aconitine, mesaconitine, hypaconitine and jesaconitine, linear calibration curves were obtained up to 500 ng/ml and the limit of detection ranged from 0.2 to 1 ng/ml. For benzoylaconine, benzoylmesaconine, benzoylhypaconine and 14-anisoylaconine, linear calibration curves were obtained up to 500 ng/ml and the limit of detection ranged from 2 to 50 ng/ml. Recoveries from serum samples were within the range 78-119% for all the compounds studied.

[Analysis of MDMA and PCP by GC-MS from patients admitted to the critical care medical center].

In our country, abuse of methamphetamine has increased. Furthermore, dealings of other drugs by using internet have increased. But, the poison cases of 3,4-methylenedioxymethamphetamine (MDMA) and phencyclidine (PCP) have never been reported in our country. We report an MDMA poison case and a PCP poison case. We could detect MDMA, MDA or PCP by GC-MS from urine and serum of patients admitted to the critical care medical center of Nippon Medical School. Case 1: A 23-year-old foreign female was admitted to our hospital because of disturbance of consciousness. Her friend said that she had been found lying on the floor of the bathroom after taking a tablet. The screening test by Triage showed AMP positive. Not methamphetamine but MDMA and MDA were detected from urine and serum of the patient by GC-MS. Case 2: A 27-year-old foreign female was admitted to our hospital because of restlessness and excitement. Her friend said that she had become restless and excited after taking 15-30 tablets of Tylenol. The screening by Triage showed BZO and PCP positive. Not acetaminophen but PCP was detected in the patient's sample by GC-MS. Drug abuse has expanded to Japan over the border. New responses to abuse drugs with respect to medical treatment and drug analyses should be established.

Optimization of inversion time for postmortem short-tau inversion recovery (STIR) MR imaging.

PURPOSE: Signal intensity and image contrast differ between postmortem magnetic resonance (PMMR) images and images acquired from the living body. We sought to achieve sufficient fat suppression with short-tau inversion recovery (STIR) PMMR imaging by optimizing inversion time (TI). MATERIAL AND METHODS: We subjected 37 deceased adult patients to PMMR imaging at 1.5 tesla 8 to 60 hours after confirmation of death and measured T1 values of areas of subcutaneous fat with relaxation time maps. Rectal temperature (RT) measured immediately after PMMR ranged from 6 to 31°C. We used Pearson's correlation coefficient to analyze the relationship between T1 and relaxation time (RT). We compared STIR images from 4 cadavers acquired with a TI commonly used in the living body and another TI calculated from the linear regression of T1 and RT. RESULTS: T1 values of subcutaneous fat ranged from 89.4 to 182.2 ms. There was a strong, positive, and significant correlation between T1 and RT (r = 0.91, P < 0.0001). The regression expression for the relationship was T1 = 2.6*RT + 90 at a field strength of 1.5T. The subcutaneous fat signal was suppressed more effectively with the optimized TI. CONCLUSION: The T1 value of subcutaneous fat in PMMR correlates linearly with body temperature. Using this correlation to determine TI, fat suppression with PMMR STIR imaging can be easily improved.

Antagonistic effects of tetrodotoxin on aconitine-induced cardiac toxicity.

Aconitine, well-known for its high cardiotoxicity, causes severe arrhythmias, such as ventricular tachycardia and ventricular fibrillation, by opening membrane sodium channels. Tetrodotoxin, a membrane sodium-channel blocker, is thought to antagonize aconitine activity. Tetrodotoxin is a potent blocker of the skeletal muscle sodium-channel isoform Na(v)1.4 (IC50 10 nM), but micromolar concentrations of tetrodotoxin are required to inhibit the primary cardiac isoform Na(v)1.5. This suggests that substantial concentrations of tetrodotoxin are required to alleviate the cardiac toxicity caused by aconitine. To elucidate the interaction between aconitine and tetrodotoxin in the cardiovascular and respiratory systems, mixtures of aconitine and tetrodotoxin were simultaneously administered to mice, and the effects on electrocardiograms, breathing rates, and arterial oxygen saturation were examined. Compared with mice treated with aconitine alone, some mice treated with aconitine-tetrodotoxin mixtures showed lower mortality rates and delayed appearance of arrhythmia. The decreased breathing rates and arterial oxygen saturation observed in mice receiving aconitine alone were alleviated in mice that survived after receiving the aconitine-tetrodotoxin mixture; this result suggests that tetrodotoxin is antagonistic to aconitine. When the tetrodotoxin dose is greater than the dose that can block tetrodotoxin-sensitive sodium channels, which are excessively activated by aconitine, tetrodotoxin toxicity becomes prominent, and the mortality rate increases because of the respiratory effects of tetrodotoxin. In terms of cardiotoxicity, mice receiving the aconitine-tetrodotoxin mixture showed minor and shorter periods of change on electrocardiography. This finding can be explained by the recent discovery of tetrodotoxin-sensitive sodium-channel cardiac isoforms (Na(v)1.1, 1.2, 1.3, 1.4 and 1.6).

Immediate non-traumatic postmortem computed tomographic demonstration of myocardial intravascular gas of the left ventricle: effects from cardiopulmonary resuscitation.

An 87-year-old man was found in a state of cardiopulmonary arrest. Despite cardiopulmonary resuscitation (CPR) for over 1 hour by emergency technicians and physicians, the patient died. Immediate postmortem computed tomography showed cardiovascular gas in the right atrium, right ventricle, and left ventricle. Cardiovascular gas in the left ventricle was located in the myocardium and appeared as linear or branch-shaped suggesting the presence of myocardial intravascular gas. This is the first report describing the appearance and significance of myocardial intravascular gas of the left ventricle as a CPR-related change.

Sudden death as a late sequel of Kawasaki disease: postmortem CT demonstration of coronary artery aneurysm.

Kawasaki disease (KD) is an acute, self-limited vasculitis of unknown etiology that primarily affects the coronary artery (CA) and presents during childhood. The characteristic coronary arterial lesion of KD is an aneurysm. Ischemic heart disease derived from a CA aneurysm is experienced approximately two decades after the onset of acute KD. In recent years, the primary issue of concern has been asymptomatic adults with a CA aneurysm caused by undiagnosed KD. We present a case of sudden death as a late KD sequel in a young adult. A postmortem CT scan revealed a coarse calcification of a left anterior descending CA aneurysm, which was confirmed at the time of autopsy. A postmortem CT scan is useful in cases of sudden death where the detection of a calcified CA aneurysm would suggest to the forensic pathologist that the deceased suffered from a late sequel of KD. The use of screening postmortem CT scans for young people may detect cases of unsuspected CA aneurysms, raising the possibility of untreated KD.

A case of fatal cervical discoligamentous hyperextension injury without fracture: correlation of postmortem imaging and autopsy findings.

We present a case of fatal cervical discoligamentous hyperextension injury without fracture. Postmortem computed tomography (PMCT) and postmortem magnetic resonance imaging (PMMRI) disclosed cervical instability and spinal cord injury in the absence of fracture, which was confirmed by autopsy. Cervical discoligamentous injury without fracture may be unnoticeable on PMCT because signs of cervical misalignment change depending on the posture of the neck at the time of postmortem imaging. Because of its greater sensitivity for soft tissue injury, PMMRI is especially useful for detecting pathological changes in cases of death due to cervical discoligamentous injury. In this paper, findings on postmortem imaging for this injury are described in detail and correlated with findings on autopsy.

Postmortem pulmonary edema: a comparison between immediate and delayed postmortem computed tomography.

OBJECTIVE: Postmortem CT (PMCT) findings may change with the passage of time after death. The aim of this study was to investigate time-dependent PMCT findings of the lung in order to aid the interpretation of postmortem images obtained at various times. MATERIALS AND METHODS: Our subjects were three non-traumatically deceased male subjects (25, 44, and 76 years old) who underwent whole body PMCT scan at two time points: one immediately after death and the other several hours after death but before the autopsy. The causes of death of the subjects were acute cardiac insufficiency (so-called sudden manhood death syndrome, 2 subjects), ischemic heart disease (acute coronary syndrome, 1 subject). The immediate and delayed PMCT findings of the lung were compared, and the differences between them were investigated. RESULTS: Compared with immediate PMCT, delayed PMCT showed advanced dependent opacity and consolidation corresponding to congestive pulmonary edema. CONCLUSION: PMCT images of the lung change as the time after death increases due to the natural postmortem changes of the corpse. Immediate PMCT is more suitable than delayed PMCT for discerning cause of death. Delayed PMCT reflects the autopsy findings more accurately than immediate PMCT.