Inconsistency between Human Observation and Deep Learning Models: Assessing Validity of Postmortem Computed Tomography Diagnosis of Drowning.

Drowning diagnosis is a complicated process in the autopsy, even with the assistance of autopsy imaging and the on-site information from where the body was found. Previous studies have developed well-performed deep learning (DL) models for drowning diagnosis. However, the validity of the DL models was not assessed, raising doubts about whether the learned features accurately represented the medical findings observed by human experts. In this paper, we assessed the medical validity of DL models that had achieved high classification performance for drowning diagnosis. This retrospective study included autopsy cases aged 8-91 years who underwent postmortem computed tomography between 2012 and 2021 (153 drowning and 160 non-drowning cases). We first trained three deep learning models from a previous work and generated saliency maps that highlight important features in the input. To assess the validity of models, pixel-level annotations were created by four radiological technologists and further quantitatively compared with the saliency maps. All the three models demonstrated high classification performance with areas under the receiver operating characteristic curves of 0.94, 0.97, and 0.98, respectively. On the other hand, the assessment results revealed unexpected inconsistency between annotations and models' saliency maps. In fact, each model had, respectively, around 30%, 40%, and 80% of irrelevant areas in the saliency maps, suggesting the predictions of the DL models might be unreliable. The result alerts us in the careful assessment of DL tools, even those with high classification performance.

A case report of forensic personal identification by transposed teeth and dental treatment marks using multidetector row computed tomography.

Using postmortem computed tomography (CT) images, we achieved personal identification of a body using transposed teeth and dental treatment marks. Transposition of teeth is a rare malpositioning anomaly. CT images can clarify the malpositioning of the teeth's roots, which is difficult to discern from gross observation of the dentition. Because dental hygiene has reduced the incidence of caries in recent years, it might be difficult to use treatment marks for personal identification in the future. Transposed teeth, although rare, provide an important clue to personal identification.

Detection of major psychoactive compounds (safrole, myristicin, and elemicin) of nutmeg in human serum via GC-MS/MS using MonoSpin® extraction: Application in a nutmeg poisoning case.

Nutmeg is an inexpensive, readily available spice used in a variety of recipes. However, the use of nutmeg powder as a recreational drug for its hallucinogenic effects is resulting in an increase in overdose rates. We encountered a male patient being hospitalized after ingesting 75 g of commercially available nutmeg powder with the intent of committing suicide. There are no available reports documenting the toxic or comatose-fatal blood concentrations or time-course of drug action in cases of nutmeg poisoning. Therefore, to improve patient management, we endeavored to determine the blood serum levels and time-course of the major psychoactive compounds (safrole, myristicin, and elemicin) present in nutmeg. We designed a simple and reliable method using the MonoSpin® extraction kit and gas chromatography-tandem mass spectrometry to detect the presence of these psychoactive compounds in human serum. The method had detection and quantitation limits of 0.14-0.16 and 0.5 ng/mL (lowest calibration points), respectively. The calibration curves displayed excellent linearity (0.996-0.997) for all three compounds at 0.5-300 ng/mL blood concentrations. The intra- and inter-day precision values for quality assurance were in the ranges of 2.4-11 % and 2.5-11 %, respectively; bias ranged from - 2.6 % to 2.1 %. Blood serum levels of safrole, myristicin, and elemicin were measured at admission (approximately 8 h post-ingestion) and approximately 94 h after a post-admission fluid therapy to evaluate their biological half-lives. We developed this method to obtain information on the psychoactive constituents of nutmeg and, thereby, determine the toxicokinetic parameters of nutmeg in a case of nutmeg poisoning.

Deep Learning-Based Diagnosis of Fatal Hypothermia Using Post-Mortem Computed Tomography.

In forensic medicine, fatal hypothermia diagnosis is not always easy because findings are not specific, especially if traumatized. Post-mortem computed tomography (PMCT) is a useful adjunct to the cause-of-death diagnosis and some qualitative image character analysis, such as diffuse hyperaeration with decreased vascularity or pulmonary emphysema, have also been utilized for fatal hypothermia. However, it is challenging for inexperienced forensic pathologists to recognize the subtle differences of fatal hypothermia in PMCT images. In this study, we developed a deep learning-based diagnosis system for fatal hypothermia and explored the possibility of being an alternative diagnostic for forensic pathologists. An in-house dataset of forensic autopsy proven samples was used for the development and performance evaluation of the deep learning system. We used the area under the receiver operating characteristic curve (AUC) of the system for evaluation, and a human-expert comparable AUC value of 0.905, sensitivity of 0.948, and specificity of 0.741 were achieved. The experimental results clearly demonstrated the usefulness and feasibility of the deep learning system for fatal hypothermia diagnosis.

A 2.5D Deep Learning-Based Method for Drowning Diagnosis Using Post-Mortem Computed Tomography.

It is challenging to diagnose drowning in autopsy even with the help of post-mortem multi-slice computed tomography (MSCT) due to the complex pathophysiology and the shortage of forensic specialists equipped with radiology knowledge. Therefore, a computer-aided diagnosis (CAD) system was developed to help with diagnosis. Most deep learning-based CAD systems only utilize 2D information, which is proper for 2D data such as chest X-ray images. However, 3D information should also be considered for 3D data like CT. Conventional 3D methods require a huge amount of data and computational cost when using 3D methods. In this article, we proposed a 2.5D method that converts 3D data into 2D images to train 2D deep learning models for drowning diagnosis. The key point of this 2.5D method is that it uses a subset to represent the whole case, covering this case as much as possible while avoiding other repetitive information. To evaluate the effectiveness of the proposed method, conventional 2D, previous 2.5D, and 3D deep learning-based methods were tested using an MSCT dataset obtained from Tohoku university. Then, to provide explainable diagnosis results, a visualization method called Gradient-weighted Class Activation Mapping was employed to visualize features relevant to drowning in CT images. Results on drowning diagnosis showed that our proposed method achieved the best performance compared to other 2D, 2.5D, and 3D methods. The visual assessment also demonstrated that our method could find the saliency regions corresponding to drowning.

Diagnosing Drowning in Postmortem CT Images Using Artificial Intelligence.

Imaging features of the lung in postmortem computed tomography (CT) scans have been reported in drowning cases. However, it is difficult for forensic pathologists with limited experience to distinguish subtle differences in CT images. In this study, artificial intelligence (AI) with deep learning capability was used to diagnose drowning in postmortem CT images, and its performance was evaluated. The samples consisted of high-resolution CT images of the chest of 153 drowned and 160 non-drowned bodies captured by an 8- or 64-row multislice CT system. The images were captured with an image slice thickness of 1.0 mm and spacing of 30 mm, and 28 images were typically captured. A modified AlexNet was used as the AI architecture. The output result was the drowning probability for each component image. To evaluate the performance of the proposed model, the area under the receiver operating characteristic curve (AUC) was analyzed, and the AUC value of 0.95 was obtained. This indicates that the proposed AI architecture is a useful and powerful complementary testing approach for diagnosing drowning in postmortem CT images. Notably, the accuracy was 81% (62/77) for cases in which resuscitation was performed, and 92% (216/236) for cases in which resuscitation was not attempted. Therefore, the proposed AI method should not be used to diagnose the cause of death when aggressive cardiopulmonary resuscitation was performed. Additionally, because honeycomb lungs are likely to exhibit different morphologies, emphysema cases should also be treated with caution when the proposed AI method is used to diagnose drowning.

Allele frequencies of 31 autosomal short tandem repeat (auSTR) loci obtained using the Precision ID GlobalFiler™ NGS STR Panel v2 in 322 individuals from the Japanese population.

In human identification methods that target short tandem repeats (STRs), massively parallel sequencing (MPS) technology has made it possible to genotype at the level of the specific sequence itself. This allows for the detection of repeat unit variants and single nucleotide polymorphisms (SNPs) adjacent to the STRs. Using the GlobalFiler™ NGS STR Panel v2, Ion S5, and Converge software, this study constructed a Japanese database of 31 autosomal STRs (auSTRs) and two sex markers from 322 individuals. After excluding some sequence errors and stutters, a total of 31 novel alleles were identified. Additionally, using the allele frequencies of 31 auSTR loci, the match probabilities for the length-based and sequence-based data were calculated to be 1.433 × 10-34 and 9.163 × 10-38, respectively. These values are at least nine orders of magnitude higher than that obtained from 21 auSTR loci in the Japanese population using the conventional capillary electrophoresis method. The database generated in this study is expected to be implemented in forensic practice and used to solve difficult casework.

Diagnostic Accuracy of Liver Damage Based on Postmortem Computed Tomography Findings in High-Energy Trauma.

The liver is an organ that is frequently injured by blunt trauma. In clinical medicine, contrast-enhanced computed tomography (CT) is useful for diagnosing liver damage. However, detection of liver injury is difficult with postmortem CT (PMCT) that does not use contrast media. This study aims to identify findings that are useful for diagnosing liver injury with PMCT. This study included 97 high-energy trauma cases that underwent both PMCT without contrast and forensic autopsy between July 2009 and November 2020. PMCT findings in and around the liver in cases of liver injury were collected. The diagnostic accuracy of each finding was calculated. Of 97 cases, 62 had liver injury on autopsy. PMCT detected hepatic surface gas in 31 cases, intrahepatic focal gas in 19 cases, high-density fluid accumulation around the liver in 12 cases, and fracture of a right lower (9th-12th) rib in 48 cases. Abnormal PMCT findings in and around the liver had insufficient diagnostic sensitivity, ranging from 19.4% to 38.7%. By contrast, the finding of a right lower rib fracture was more sensitive for suspected liver injury. Our results indicate that abdominal liver findings (hepatic surface gas, intrahepatic focal gas, and high-density fluid accumulation around the liver) are of limited utility for the diagnosis of liver injury, whereas a right lower rib fracture is a useful indirect finding.

Cervical intervertebral separation caused by trauma on post-mortem computed tomography: Possibility of a diagnosis based on intervertebral gas.

OBJECTIVES: Gas is a common finding in cervical intervertebral separation. However, intervertebral gas is also found in many decedents without intervertebral separation. Here, we quantified intervertebral gas and examined its value in the diagnosis of cervical intervertebral separation. METHODS: We retrospectively reviewed data from 1118 decedents who underwent post-mortem computed tomography (CT) and autopsy from May 2011 to July 2016 and selected those with cervical intervertebral gas with or without intervertebral separation. These data comprised 56 cervical intervertebral spaces with gas [intervertebral separation in 19 (33.9%)] in 43 subjects [intervertebral separation in 17 (39.5%)]. We categorised the decedents according to gas volume, position, and shape and determined the significance of the differences between the decedents with and without separation. RESULTS: The gas volume did not differ significantly between decedents with and without separation (p = 0.063). However, there were significant differences in the gas position between decedents with and without separation. In the sagittal plane: gas was seen in the "centred" position in the ventral-to-dorsal direction in more decedents without separation than in those with separation (p = 0.018). Gas was seen in the ventral-to-dorsal positions in more decedents with separation than in those without separation (p = 0.049). In the cranio-caudal direction, gas in the upper position was more common in decedents with separation than in those without separation in the sagittal plane (p = 0.03). In the coronal plane: gas was seen in the upper position more frequently in decedents with separation in the cranio-caudal direction than in those without separation (p = 0.001). A significant difference in gas shape was observed only in the coronal plane (p = 0.024); irregular gas was associated with decedents without separation. CONCLUSION: Gas in the ventral-to-dorsal and upper positions in the sagittal plane and in the upper position in the coronal plane was rather indicative of cervical intervertebral separation. An irregular gas shape in the coronal plane was indicative of degenerative changes.

Evaluation of the Utility of Mitochondrial DNA Testing in Personal Identification Work in the Great East Japan Earthquake of 2011.

Although the Great East Japan Earthquake occurred on March 11, 2011, identification of victims is still ongoing. Typically, mitochondrial DNA (mtDNA) is performed when it is difficult to identify an individual using nuclear DNA. In Japan, samples from criminal investigations are subjected to nuclear DNA testing at the Scientific Research Institute belonging to each prefectural police headquarters, while all mtDNA tests were originally conducted at the National Research Institute of Police Science. However, the appraisal work using mtDNA became more time-consuming as the number of target samples increased. Because our department is capable of performing mtDNA testing, the Miyagi Prefectural Police requested that our department perform mtDNA testing. Specifically, we focused on 16 individuals as putative candidates for 11 unidentified human remains; efforts to identify these remains were performed using samples from 20 relatives. These efforts positively identified six victims. This included confirmation that one corpse had originally been identified incorrectly. Although disasters of a similar scale can strike Japan again, there are limited facilities that can consistently perform mtDNA testing. Expensive sequencing machines and properly trained operators are essential for mtDNA testing, but they cannot be established at the forensic departments of all medical schools. There is thus an urgent need to establish core facilities at appropriate sites, such as Tohoku University in the Tohoku Region, to build a mtDNA testing system suitable for the aftermath of any disaster.

Block-like and cast-like hyperdense areas in the right heart cavities on post-mortem CT strongly suggest the presence of intracardiac blood clots at autopsy.

OBJECTIVE: To classify the types of hyperdense areas in the heart cavities on post-mortem CT (PMCT) and compare them according to the presence of blood clots in the heart cavities at forensic autopsy. METHODS: One hundred and twelve cases with CT images taken before forensic autopsy were evaluated. The presence and shape of hyperdense areas in the right or left heart cavities were retrospectively evaluated on PMCT images and were classified into four types (block-like, cast-like, fluid level-like, and unclear). The presence of blood clots was confirmed when there were clots in the heart cavities at forensic autopsy. RESULTS: Of the 112 cases, 57 exhibited blood clots in the heart cavities at forensic autopsy. The hyperdense areas in the right heart cavities on PMCT in 57 cases exhibiting blood clots at forensic autopsy were classified as follows: block-like, 32; fluid level-like, 4; cast-like, 17; and unclear, 4. The sensitivity of block-like and cast-like hyperdense areas in the right heart cavities on PMCT for the presence of clots in the heart cavities at forensic autopsy was 86% (95% confidence interval [CI]: 74-94%); the corresponding specificity, PPV, and NPV were 95% (95% CI: 85-99%), 94% (95% CI: 84-99%), and 87% (95% CI: 75-94%), respectively. CONCLUSION: Block-like and cast-like hyperdense areas in the right heart cavities on PMCT predicted the presence of intracardiac blood clots at forensic autopsy. KEY POINTS: • Clinical radiologists likely have no experience of interpreting findings of blood clots on post-mortem CT (PMCT). • The appearance of blood clots on PMCT provides important clues for diagnosing the cause and process of death. • The shapes of the hyperdense areas in the heart cavities were classified into four types, and two of these types could be used to predict the presence of blood clots in the heart cavities at forensic autopsy.

LC-MS/MS method for rapid and accurate detection of caffeine in a suspected overdose case.

Excessive intake of caffeine, otherwise known to be a safe and mild central nervous system stimulant, causes nausea, vomiting, convulsions, tachycardia, and eventually fatal arrhythmias and death. Caffeine intoxication, a global problem, has been increasing in Japan since 2013. Thus, there is a need for rapid and accurate diagnosis of caffeine poisoning in forensic and clinical toxicology investigations. Herein, we demonstrate rapid and accurate caffeine quantitation by liquid chromatography tandem mass spectrometry using the standard addition method in a fatal case. Biological samples were diluted 500-100,000-fold and subjected to a simple pretreatment (adding caffeine standard and internal standard and passing through a lipid removal cartridge). The multiple reaction monitoring transitions were 195 â†’ 138 for quantitation, 195 â†’ 110 for the qualifier ion, and 204 â†’ 144 for the internal standard (caffeine-d9). The standard plots were linear over 0-900 ng/mL (r2 = 0.9994-0.9999) for biological samples, and the reproducibility (%RSD) of the method was 1.53-6.97% (intraday) and 1.59-10.4% (interday). Fatal levels of caffeine (332 µg/mL) and toxic to fatal levels of olanzapine (625 ng/mL), along with other pharmaceuticals were detected in the external iliac venous blood. The cause of death was determined to be multi-drug poisoning, predominantly caused by caffeine. Our method is useful for not only forensic cases but also the rapid diagnosis of caffeine overdose in emergency clinical settings.

A Deep Learning Aided Drowning Diagnosis for Forensic Investigations using Post-Mortem Lung CT Images.

Feasibility of computer-aided diagnosis (CAD) systems has been demonstrated in the field of medical image diagnosis. Especially, deep learning based CAD systems showed high performance thanks to its capability of image recognition. However, there is no CAD system developed for post-mortem imaging diagnosis and thus it is still unclear if the CAD system is effective for this purpose. Particulally, the drowning diagnosis is one of the most difficult tasks in the field of forensic medicine because findings of the post-mortem image diagnosis are not specific. To address this issue, we develop a CAD system consisting of a deep convolution neural network (DCNN) to classify post-mortem lung computed tomography (CT) images into two categories of drowning and non-drowning cases. The DCNN was trained by means of transfer learning and performance evaluation was conducted by 10-fold cross validation using 140 drowning cases and 140 non-drowning cases of the CT images. The area under the receiver operating characteristic curve (AUC-ROC) for the DCNN was achieved 0.88 in average. This high performance clearly demonstrated that the proposed DCNN based CAD system has a potential for post-mortem image diagnosis of drowning.

An ultra-rapid drug screening method for acetaminophen in blood serum based on probe electrospray ionization-tandem mass spectrometry.

Poisoning incidents caused by drugs, accidental ingestion of poisons, attempted suicide, homicide, and exposure to toxic compounds occur frequently every year across the globe. This raises the need to rapidly identify toxic agents in poisoned patients in a clinical emergency setting. In addition, determining drug/poison concentration is undoubtedly necessary to arrive at a toxicological treatment plan. The purpose of this study was to develop an ultra-rapid drug screening method for the clinical treatment of poisoning. Probe electrospray ionization (PESI), one of the ambient ionization techniques, is able to detect compounds from various biological materials almost directly. We applied the PESI technique to the rapid detection of acetaminophen (APAP). Blood serum samples were diluted 100-fold with 10 mM ammonium formate/ethanol (1:1 v/v) solution including deuterium-labeled internal standards (IS; APAP-d4). Only 10 µL of the diluted sample was used for measurement. The tandem mass spectrometer (MS/MS) equipped with a PESI was used in selected reaction monitoring mode for the quantitation of APAP; the measurement time was only 18 s. Transitions were set at 152 > 110 for quantitation, 152 > 65 for qualifier, and 156 > 114 for IS (APAP-d4). All measurements were conducted in positive mode. The calibration curve (1/x2) was linear over the range of 1.56-200 µg/mL (r2 = 0.998), and the limit of detection and quantitation were 0.37 µg/mL and 1.56 µg/mL, respectively. The accuracy (bias) and precision (RSD%) of the method were within an acceptable range (-0.15-2.8% and 2.3-6.1%, respectively) and matrix effect at 3 concentrations (95.1-104%) indicated that PESI-MS/MS is only slightly affected by matrices. In real forensic cases, quantitative values of APAP determined by the PESI-MS/MS were almost identical to those determined by the liquid chromatography-MS/MS method. Since PESI-MS/MS is a simple, reliable, and rapid determination method for toxic agents with virtually no need for blood serum pre-treatment, it would be highly suitable for poisoning cases in clinical emergency settings. In the future, a method for simultaneous rapid determination of multiple toxic agents will be developed.

A fast paraquat quantitation method in human serum using probe electrospray ionization-tandem mass spectrometry for emergency settings.

INTRODUCTION: Paraquat (PQ) is one of the most toxic herbicides to humans. However, it is still in use in many countries, including Japan, and many incidents, such as homicides, intentional ingestions, and occupational accidents, have been reported thus far. In PQ poisoning cases, it is possible to predict severity and prognosis using nomograms. Therefore, if the serum PQ level is determined immediately, a treatment plan can be rapidly established. However, most known analytical methods are time-consuming and therefore hardly ever contribute to patient treatment. METHODS: We developed a new method for PQ quantitation in serum by combining a probe electrospray ionization technique with mass spectrometry. This method requires virtually no serum pretreatment and can yield quantitation values in 18 s. RESULTS: We applied the proposed method to samples from real poisoning cases and compared the results with those obtained via liquid-chromatography-tandem mass spectrometry, revealing the absence of any significant differences at the 5% significance level (t(8) = 1.000, p > .05). The limits of detection and quantitation were 0.004 and 0.015 µg/L, respectively, and the calibration curve exhibited good linearity over the concentration range of 0.015-4.0 µg/mL (r2 = 0.998). DISCUSSION: As the proposed method is fast and easy to perform, it should be useful in emergency medical settings.

Application of probe electrospray ionization-tandem mass spectrometry to ultra-rapid determination of glufosinate and glyphosate in human serum.

Glufosinate and glyphosate, which are non-selective herbicides that include an amino acid moiety in their structures, are frequently used worldwide to control unwanted vegetation. Unfortunately, these readily available herbicides are also used by people to commit suicide, and thus represent important chemicals of interest in the fields of clinical medicine and forensics. Because of the high water solubility of these herbicides, most analytical methods for their detection require a derivatization step, which results in longer analysis times. Therefore, derivatization-based methods do not currently contribute to judgements on treatment decisions in emergency medicine. In this study, we addressed this limiting factor by developing an ultra-rapid and simple analytical technique using a combination of probe electrospray ionization (PESI) and tandem mass spectrometry (MS/MS), which gives quantitative results within 0.3 min. Herbicide standards were added to human serum that was then subjected to analysis (N = 5 per concentration). The analysis was repeated daily over eight consecutive days. The limit of detection (LOD) was 0.59 µg/mL for glufosinate and 0.20 µg/mL for glyphosate. The limit of quantitation (LOQ), i.e., the lowest point on the calibration curves, was 1.56 µg/mL for both the herbicides. The matrix effects were observed at three different concentrations (between 95.7%-104% for glufosinate, and between 90.7%-95.7% for glyphosate). When applied to samples taken from actual poisoning cases (six samples for each herbicide), the present method gave almost the same quantitative values as those obtained by conventional high-performance liquid chromatography with fluorescence detection. Thus, we believe that PESI-MS/MS could emerge as a rapid diagnosis method in the clinical emergency field.

A quantitative morphological analysis of three-dimensional CT coxal bone images of contemporary Japanese using homologous models for sex and age estimation.

Sexual dimorphisms and age-dependent morphological features of the human coxal bone were quantitatively analyzed using homologous models created from three-dimensional (3D) computed tomography images of the pelvis (male: 514 samples, female: 388 samples, age 16-100). Bilateral average coxal images of each sex and age decade were generated separately through principle component analyses (PCA). By measuring average point-to-point distances of 8472 corresponding points (average corresponding point differences [ACPDs]) between each homologous coxal image and the average images, the sex of more than 93% of the samples was correctly assigned. Some principal components (PCs) detected in PCA of the homologous models of the samples correlated fairly well with age and are affected by features of the curvature of the iliac crest, the arcuate line and the greater sciatic notch. Moreover, separate PCA using the average images of each age decade successfully detected the first PCs, which were strongly correlated with age. However, neither multiple regression analysis using PCs related to age nor comparison of ACPDs with the average images of each age decade could produce accurate results for age decade assignment of unknown (blind) samples. Therefore, more detailed analysis of age-dependent morphological features would be necessary for actual age estimation. In addition, some laterality or left and right shape difference of the coxal bone images was also elucidated, and was more significant in females. Analysis of 3D structures using homologous models and PCA appears to be a potential technique to detect subsistent morphological changes of bones.

Direct detection of the psychoactive substance MT-45 in human tissue samples by probe electrospray ionization-tandem mass spectrometry.

Analyses of drugs and poisons in tissue samples are essential in forensic toxicology and pharmacology. However, current procedures for tissue analysis are laborious and time-consuming. Therefore, we assessed the utility of a newly devised probe electrospray ionization (PESI) technique with tandem mass spectrometry (MS/MS) for easy, ultra-rapid drug detection in human tissue samples. Using this system, typical pretreatment procedures, such as solid-phase extraction, liquid-liquid extraction, deproteinization, or homogenization, can be avoided. Briefly, a tissue sample of 1-2 mm3 was supplemented with a solution of ethanol and 10 mmol/L ammonium formate, and measurements were obtained. We demonstrated the successful application of this method in a forensic case by detecting an opioid analgesic, MT-45, in all tissue samples (liver, kidney, lung, brain, and heart). We also detected oxidized metabolites of MT-45 in the liver. Since the analysis required only 0.5 minutes per sample, PESI-MS/MS is an ultra-rapid detection method. Furthermore, for a quantitative approach, the total analysis time for the combination of PESI-MS/MS with the quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method (from instrument start-up to extraction and PESI-analysis) was within 8 minutes. MT-45 concentrations obtained by QuEChERS-PESI-MS/MS and liquid chromatography (LC) -MS/MS were similar for all tissue samples. PESI-MS/MS cannot be used to separate isobars/isomers (ie, compounds with the same m/z value), similar to other direct introduction techniques. Further studies are needed to validate the quantitation method. However, our results indicate that PESI-MS/MS is a potentially easy and rapid technique for the analysis of drugs and poisons in human tissue samples.

Identification of 5-Fluoro ADB in Human Whole Blood in Four Death Cases.

Four deaths that seemed to have been caused by a designer drug occurred within a 3-week period in Sendai, Japan. In each case, the decedent possessed the same sachet, labeled "Heart Shot BLACK", which contained a dried plant material with an aromatic scent. It was revealed in our analysis that the product contained a synthetic cannabinoid receptor agonist, 5-fluoro ADB (methyl 2-[1-(5-fluoropentyl)-1H-indazole-3-carboxamide]-3,3-dimethylbutanoate, also known as 5-fluoro MDMB-PINACA), which is now classified as a restricted designer drug in Japan after it caused several casualties. For standard samples, the detection of 5-fluoro ADB in whole blood in the calibration range (0.04-4 ng/mL) was successful with recoveries of 94.6-98.1%, limits of detection of 6 pg/mL, and limits of quantification of 40 pg/mL. The intraday and interday precisions were 0.9-4.8% and 1.1-6.6%, respectively. The bias was -1.1 to 2.9%. We were able to confirm that 5-fluoro ADB was present in the blood of all four decedents at a concentration of 0.11-1.92 ng/mL. From the autopsy, toxicological findings, and circumstances surrounding the cases, it was considered that inhalation of 5-fluoro ADB could have contributed to the deaths. However, the extent to which 5-fluoro ADB contributed to the deaths remains unclear due to the current lack of toxicological information on the compound. In future research, the toxicity of 5-fluoro ADB in humans and the mechanism underlying this effect need to be elucidated.

Sudden death in a child caused by a giant cavernous hemangioma of the anterior mediastinum.

A 4-year-old girl who had been treated for asthma since the age of 2 years had a severe coughing fit and died suddenly. The patient had a history of occasional severe coughing fits, and these fits had been worsening in severity during the week before her death. Prior to death, she was taken to a clinician, and thymic hypertrophy was suspected based on chest X-ray findings. The clinician recommended that she visit a general hospital at a later date; however, she died that night. Postmortem radiology and autopsy revealed a large mass in the anterior mediastinum compressing the heart and airway, and no other findings attributable to sudden death were observed. Therefore, we concluded that the patient's death was attributable to acute respiratory and cardiac circulatory failure secondary to the pressure induced by the mass. Microscopically, the mass showed a cavernous structure composed of cystically dilated, thin-walled large vessels filled with blood. The final diagnosis was a cavernous hemangioma. Hemangiomas are the most common benign vascular anomalies seen in young children; however, mediastinal hemangiomas are rare and can cause life-threatening complications because of their size and location. Therefore, forensic pathologists should include hemangioma as a differential diagnosis in children with anterior mediastinal masses.