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.

Fibroblast Growth Factor-21, Leptin, and Adiponectin Responses to Acute Cold-Induced Brown Adipose Tissue Activation.

BACKGROUND: Adipocyte-derived hormones play a role in insulin sensitivity and energy homeostasis. However, the relationship between circulating fibroblast growth factor 21 (FGF21), adipocytokines and cold-induced supraclavicular brown adipose tissue (sBAT) activation is underexplored. OBJECTIVE: Our study aimed to investigate the relationships between cold-induced sBAT activity and plasma FGF21 and adipocytokines levels in healthy adults. DESIGN: Nineteen healthy participants underwent energy expenditure (EE) and supraclavicular infrared thermography (IRT) within a whole-body calorimeter at baseline and at 2 hours post-cold exposure. 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scans were performed post-cold exposure. PET sBAT mean standardized uptake value (SUV mean), MR supraclavicular fat fraction (sFF), anterior supraclavicular maximum temperature (Tscv max) and EE change (%) after cold exposure were used to quantify sBAT activity. MAIN OUTCOME MEASURES: Plasma FGF21, leptin, adiponectin, and tumor necrosis factor alpha (TNFα) at baseline and 2 hours post-cold exposure. Body composition at baseline by dual-energy x-ray absorptiometry (DXA). RESULTS: Plasma FGF21 and adiponectin levels were significantly reduced after cold exposure in BAT-positive subjects but not in BAT-negative subjects. Leptin concentration was significantly reduced in both BAT-positive and BAT-negative participants after cold exposure. Adiponectin concentration at baseline was positively strongly associated with sBAT PET SUV mean (coefficient, 3269; P = 0.01) and IRT Tscv max (coefficient, 6801; P  = 0.03), and inversely correlated with MR sFF (coefficient, -404; P  = 0.02) after cold exposure in BAT-positive subjects but not in BAT-negative subjects. CONCLUSION: Higher adiponectin concentrations at baseline indicate a greater cold-induced sBAT activity, which may be a novel predictor for sBAT activity in healthy BAT-positive adults. HIGHLIGHTS: A higher adiponectin concentration at baseline was associated with higher cold-induced supraclavicular BAT PET SUV mean and IRT Tscv max, and lower MR supraclavicular FF. Adiponectin levels maybe a novel predictor for cold-induced sBAT activity.

Using a multimodal near-infrared spectroscopy and MRI to quantify gray matter metabolic rate for oxygen: A hypothermia validation study.

Non-invasive quantitative imaging of cerebral oxygen metabolism (CMRO2) in small animal models is crucial to understand the role of oxidative metabolism in healthy and diseased brains. In this study, we developed a multimodal method combining near-infrared spectroscopy (NIRS) and MRI to non-invasively study oxygen delivery and consumption in the cortex of mouse and rat models. The term CASNIRS is proposed to the technique that measures CMRO2 with ASL and NIRS. To determine the reliability of this method, CMRO2 values were compared with reported values measured with other techniques. Also, the sensitivity of the CASNIRS technique to detect changes in CMRO2 in the cortex of the animals was assessed by applying a reduction in core temperature, which is known to reduce CMRO2. Cerebral blood flow (CBF) and CMRO2 were measured in five mice and five rats at a core temperature of 37 °C followed by another measurement at 33 °C. CMRO2 was 7.8 ±â€¯1.8 and 3.7 ±â€¯0.9 (ml/100 g/min, mean ±â€¯SD) in mice and rats respectively. These values are in good agreement with reported values measured by 15O PET, 17O NMR, and BOLD fMRI. In hypothermia, we detected a significant decrease of 37% and 32% in CMRO2 in the cortex of mice and rats, respectively. Q10 was calculated to be 3.2 in mice and 2.7 in rats. In this study we showed that it is possible to assess absolute values of metabolic correlates such as CMRO2, CBF and oxygen extraction fraction (OEF) noninvasively in living brain of mice and rats by combining NIRS with MRI. This will open new possibilities for studying brain metabolism in patients as well as the many mouse/rat models of brain disorders.

Visceral fat, but not subcutaneous fat, is associated with lower core temperature during laparoscopic surgery.

BACKGROUND: Previous studies suggest that lower BMI is a risk factor for intraoperative core hypothermia. Adipose tissue has a high insulation effect and is one of the major explanatory factors of core hypothermia. Accordingly, determining the respective influence of visceral and subcutaneous fat on changes in core temperature during laparoscopic surgery is of considerable interest. METHODS: We performed a prospective study of 104 consecutive donors who underwent laparoscopic nephrectomy. Temperature data were collected from anesthesia records. Visceral and subcutaneous fat were calculated by computed tomography (CT) or ultrasound. For ultrasound measurements, preperitoneal fat thickness was used as an index of visceral fat. Multiple linear regression analysis was performed at 30, 60, and 120 minutes after the surgical incision to identify the predictive factors of body temperature change. The potential explanatory valuables were age, sex, BMI, visceral fat, and subcutaneous fat. RESULTS: BMI (ß = 0.010, 95%CI: 0.001-0.019, p = 0.033) and waist-to-hip ratio (ß = 0.424, 95%CI: 0.065-0.782, p = 0.021) were associated with increased core temperature at 30 minutes after the surgical incision. Ultrasound measured-preperitoneal fat was significantly associated with increased core temperature at 30 and 60 minutes after the surgical incision (ß = 0.012, 95%CI: 0.003-0.021, p = 0.009 and ß = 0.013, 95%CI: 0.002-0.024, p = 0.026). CT-measured visceral fat was also associated with increased core temperature at 30 minutes after the surgical incision (ß = 0.005, 95%CI: 0.000-0.010, p = 0.046). Conversely, subcutaneous fat was not associated with intraoperative core temperature. Male sex and younger age were associated with lower intraoperative core temperature. CONCLUSIONS: Visceral fat protects against core temperature decrease during laparoscopic donor nephrectomy.

ACR Appropriateness Criteria® Sudden Onset of Cold, Painful Leg.

Acute limb ischemia (ALI) requires urgent diagnosis and treatment to prevent limb loss. Invasive digital subtraction arteriography (DSA) is the gold standard for diagnosing ALI. DSA is the only diagnostic modality that permits simultaneous treatment of acute arterial occlusion. Noninvasive imaging with MRA or CT angiography may also be appropriate before treatment, especially when the diagnosis of ALI is in doubt or where DSA is unavailable. Other imaging and noninvasive physiologic tests may prove important for longer term management but are less recommended in the acute setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Good neurological outcome after accidental hyopthermia presenting with asytole.

A 43-year-old woman became exhausted and fainted on descent at 1127 MAMSL altitude and snowfall. A rescue team diagnosed asystole. With manual cardiopulmonary resuscitation (CPR) she was transported to the next extracorporeal life support (ECLS) center. Admission temperature was 20.7 °C. CPR continued until ECLS was initiated. Two days later she was awake, orientated, and with no neurological deficits. With hypothermic cardiac arrest, a favorable outcome depends on early continuous CPR, triage, and ECLS rewarming. It holds true that "nobody is dead until they are warmed and dead" if one cools first and arrests thereafter.

[Case report: resuscitation of a hypothermic patient - "Nothing's like it seems!"]. / Kasuistik: Reanimation eines hypothermen Patienten - "Nichts ist so, wie es scheint!"

We report about a prolonged resuscitation of a hypothermic patient (26.2°C) in stadium HT III of the Swiss Staging System (SSS). A mechanical chest compression with the Lund University Cardiac Assist System (LUCAS) and the rewarming with a haemodialysis device were implemented. After a resuscitation time of 200min and a body temperature of 32.1°C ventricular fibrillation occurred. After the defibrillation a return of spontaneous circulation (ROSC) was established. The patient achieved a very good cognitive-mnestic result after the resuscitation but he suffered a neurological deficit in the meaning of paraplegia.

Postmortem pulmonary CT in hypothermia.

Fatal hypothermia has been associated with pulmonary edema. With postmortem full body computed tomography scanning (PMCT), the lungs can also be examined for CT attenuation. In fatal hypothermia cases low CT attenuation appeared to prevail in the lungs. We compared 14 cases of fatal hypothermia with an age-sex matched control group. Additionally, 4 cases of carbon monoxide (CO) poisoning were examined. Furthermore, 10 test cases were examined to test predictability based on PMCT. Two readers measured CT attenuation on four different axial slices across the lungs (blinded to case group and other reader's results). Hypothermia was associated with statistically significantly lower lung PMCT attenuation and lower lung weights than controls, and there was a dose-effect relationship at an environmental temperature cutoff of 2 °C. CO poisoning yielded low pulmonary attenuation but higher lung weights. General model based prediction yielded a 94% probability for fatal hypothermia deaths and a 21% probability for non-hypothermia deaths in the test group. Increased breathing rate is known to accompany both CO poisoning and hypothermia, so this could partly explain the low PMCT lung attenuation due to an oxygen dissociation curve left shift. A more marked distension in fatal hypothermia, compared to CO poisoning, indicates that further, possibly different mechanisms, are involved in these cases. Increased dead space and increased stiffness to deflation (but not inflation) appear to be effects of inhaling cold air (but not CO) that may explain the difference in low PMCT attenuation seen in hypothermia cases.

Postmortem computed tomography lung findings in fatal of hypothermia.

To identify lung findings specific to fatal hypothermia on postmortem computed tomography (CT) imaging. Whole body CT scans were performed followed by full autopsy to investigate causes of death. There were 13 fatal hypothermia cases (group A) and 118 with other causes of death (group B). The chest cavity (CC), dead space including fluid/pneumothorax (DS), aerated lung volume (ALV), percentage aerated lung (%ALV), and tracheal aerated volume (ATV) were measured. Autopsy findings of groups A and B were compared. Receiver operating characteristics (ROC) curves were used to identify factors specific to fatal hypothermia. There were no differences in age, sex, number with emphysema, or time from death to CT examination between the 2 groups. CC, DS, ALV, %ALV, and ATV were 2601.0±247.4 (mL), 281.1±136.5 (mL), 1564.5±281.1 (mL), 62.1±6.2(%), and 21.8±2.7 (mL) in group A and 2339.2±67.7 (mL), 241.1±38.0 (mL), 739.9±67.0 (mL), 31.4±2.3(%), and 15.9±0.8 (mL) in group B, respectively. There were statistically significant differences between groups A and B in ALV, %ALV and ATV. The multiple comparison procedure revealed that ALV and %ALV differed significantly between fatal hypothermia and other causes of death (p<0.05). Using ROC evaluation, %ALV had the largest area under the curve (0.819). This study demonstrates that the %ALV is greater in fatal hypothermia cases than in those with other causes of death on postmortem CT chest imaging. Based on CT, hypothermia is very likely to be the cause of death if the %ALV is >70%.

Insights into thermoregulation: a clinico-radiological description of Shapiro syndrome.

Shapiro syndrome is a rare entity, comprising a triad of recurrent hypothermia, hyperhidrosis and congenital agenesis of the corpus callosum. Fewer than 50 cases have been described, almost invariably in patients presenting in childhood or early adulthood. We present a case of an 80 year old woman presenting with recurrent bouts of shivering, sweating and profound malaise, who sought medical attention because the frequency and severity of attacks worsened in her later years. MRI Brain demonstrated agenesis of the corpus callosum; a rigorous work-up excluded other causes for her symptomatology. The intricate interplay of neuronal networks involved in thermoregulation remains to be fully elucidated and as such, little is known about the pathophysiological mechanisms underlying the clinical manifestations of Shapiro syndrome. We present novel data from FDG-PET imaging of our patient, demonstrating hypermetabolism in a number of brainstem and cerebellar regions during the symptomatic phase. These findings imply that aberrant thermoregulation in Shapiro syndrome involves a number of structures remote from the callosal region. We also present neuropsychometric findings in our patient, of which there have been no reports to date. We postulate that the ageing brain may be more susceptible to the paroxysmal neurochemical fluxes implicated in the syndrome.

Quantitative analysis of pulmonary pathophysiology using postmortem computed tomography with regard to the cause of death.

Radiological lung transparency depends on the air contents involved in respiratory function. The present study quantitatively investigated postmortem lung air distribution in forensic autopsy cases (n=135) using computed tomography (CT) to analyze cardiopulmonary pathophysiology in the death process, involving emphysema, congestion and edema. Combined analyses of the CT morphology and attenuation value (Hounsfield unit, HU) of the bilateral lungs, with reference to histopathology, could categorize CT findings (10-90 percentile mode/mean HU values) with regard to the causes of death as follows: (I) hyperaeration (mode/mean HU below -760/-560: emphysema) for obstructive pulmonary disease, starvation and hypothermia (cold exposure); (II) mostly normal aeration with partial ground glass opacification (mode/mean HU, -850 to -360/-700 to -380: partial congestion and edema), consisting of subtype II-a with peri-bronchial/-vascular opacity for mechanical asphyxia, drowning and fire fatality, and subtype II-b with decreased vascularity for gunshot head injury, cerebrovascular disease and hemopericardium; (III) hypoaeration to airless with predominant hypostatic ground glass opacification (mode/mean HU, -870 to 0/-720 to -200: mottled hypostatic congestion and edema) for blunt head/neck injury, intoxication, hyperthermia (heat stroke) and congestive heart failure; (IV) hypoaeration to airless with predominant hypostatic consolidation (mode/mean HU, -790 to 0/-520 to -70: intense hypostatic congestion with edema) for acute ischemic heart disease; and (V) airless to consolidated (mode/mean HU over -420/-370: segmental or multiple patchy consolidations with edema) for pneumonia. Mode HU represents the major alveolar status, while the mean HU reflects the whole lung air contents. CT data analysis is useful for quantitative evaluation of pulmonary pathology as a supplementary procedure.

Ketorolac alters blood flow during normothermia but not during hyperthermia in middle-aged human skin.

In young healthy humans full expression of reflex cutaneous vasodilation is dependent on cyclooxygenase (COX)- and nitric oxide synthase (NOS)-dependent mechanisms. Chronic low-dose aspirin therapy attenuates reflex cutaneous vasodilation potentially through both platelet and vascular COX-dependent mechanisms. We hypothesized the contribution of COX-dependent vasodilators to reflex cutaneous vasodilation during localized acute COX inhibition would be attenuated in healthy middle-aged humans due to a shift toward COX-dependent vasoconstrictors. Four microdialysis fibers were placed in forearm skin of 13 middle-aged (53 +/- 2 yr) normotensive healthy humans, serving as control (Ringer), COX-inhibited (10 mM ketorolac), NOS-inhibited (10 mM N(G)-nitro-l-arginine methyl ester), and combined NOS- and COX-inhibited sites. Red blood cell flux was measured over each site by laser-Doppler flowmetry as reflex vasodilation was induced by increasing oral temperature (T(or)) 1.0 degrees C using a water-perfused suit. Cutaneous vascular conductance was calculated (CVC = flux/mean arterial pressure) and normalized to maximal CVC (CVC(max); 28 mM sodium nitroprusside). CVC(max) was not affected by localized microdialysis drug treatment (P > 0.05). Localized COX inhibition increased baseline (18 +/- 3%CVC(max); P < 0.001) compared with control (9 +/- 1%CVC(max)), NOS-inhibited (7 +/- 1%CVC(max)), and combined sites (10 +/- 1%CVC(max)). %CVC(max) in the COX-inhibited site remained greater than the control site with DeltaT(or) < or = 0.3 degrees C; however, there was no difference between these sites with DeltaT(or) > or = 0.4 degrees C. NOS inhibition and combined COX and NOS inhibition attenuated reflex vasodilation compared with control (P < 0.001), but there was no difference between these sites. Localized COX inhibition with ketorolac significantly augments baseline CVC but does not alter the subsequent skin blood flow response to hyperthermia, suggesting a limited role for COX-derived vasodilator prostanoids in reflex cutaneous vasodilation and a shift toward COX-derived vasoconstrictors in middle-aged human skin.

Spontaneous periodic hypothermia and hyperhidrosis.

We present a patient diagnosed with Shapiro syndrome without corpus callosum agenesis. A 4-year-old-girl was admitted to the hospital with complaints of sweating, cooling, and drowsiness that continued during the last week of her admission. Attacks occurred almost daily, and lasted for about 1 hour. All laboratory findings, as well as Holter and echocardiography results, were normal. Cranial magnetic resonance imaging demonstrated an intact corpus callosum, and electroencephalography obtained during an attack revealed normal findings. However, technetium 99m-labeled hexamethylpropylene amine oxime brain single-photon emission computed tomography indicated increased perfusion in the right thalamus, basal ganglia, and inferior frontal areas during a hypothermic period. Although oxcarbazepine reduced the frequency of attacks, they were not halted completely. The patient responded better to carbamazepine.

Cold exposure-induced rhabdomyolysis demonstrated by bone scintigraphy.

This report describes a case of acute renal failure due to rhabdomyolysis that developed after prolonged exposure to cold. A 47-year-old man visited a mountain during winter wearing only casual clothes and became lost at temperatures below freezing for 8 hours. Upon admission, the patient complained of a tingling sensation and numbness in the both upper and lower extremities with anuria. The serum blood urea nitrogen, creatinine, creatinine kinase, and myoglobin levels were elevated. Bone scintigraphy on the second day revealed increased activity in the superficial muscle groups in the abdomen, back, buttock, thighs, legs, and arms, which was compatible with rhabdomyolysis.