In situ temperature determination using magnetic resonance spectroscopy thermometry for noninvasive postmortem examinations.

Magnetic resonance spectroscopy (MRS) thermometry offers a noninvasive, localized method for estimating temperature by leveraging the temperature-dependent chemical shift of water relative to a temperature-stable reference metabolite under suitable calibration. Consequentially, this technique has significant potential as a tool for postmortem MR examinations in forensic medicine and pathology. In these examinations, the deceased are examined at a wide range of body temperatures, and MRS thermometry may be used for the temperature adjustment of magnetic resonance imaging (MRI) protocols or for corrections in the analysis of MRI or MRS data. However, it is not yet clear to what extent postmortem changes may influence temperature estimation with MRS thermometry. In addition, N-acetylaspartate, which is commonly used as an in vivo reference metabolite, is known to decrease with increasing postmortem interval (PMI). This study shows that lactate, which is not only present in significant amounts postmortem but also has a temperature-stable chemical shift, can serve as a suitable reference metabolite for postmortem MRS thermometry. Using lactate, temperature estimation in postmortem brain tissue of severed sheep heads was accurate up to 60 h after death, with a mean absolute error of less than 0.5°C. For this purpose, published calibrations intended for in vivo measurements were used. Although postmortem decomposition resulted in severe metabolic changes, no consistent deviations were observed between measurements with an MR-compatible temperature probe and MRS thermometry with lactate as a reference metabolite. In addition, MRS thermometry was applied to 84 deceased who underwent a MR examination as part of the legal examination. MRS thermometry provided plausible results of brain temperature in comparison with rectal temperature. Even for deceased with a PMI well above 60 h, MRS thermometry still provided reliable readings. The results show a good suitability of MRS thermometry for postmortem examinations in forensic medicine.

Neurometabolic profile of the amygdala in smokers assessed with 1H-magnetic resonance spectroscopy.

Tobacco smoking is one of the main causes of premature death worldwide and quitting success remains low, highlighting the need to understand the neurobiological mechanisms underlying relapse. Preclinical models have shown that the amygdala and glutamate play an important role in nicotine addiction. The aims of this study were to compare glutamate and other metabolites in the amygdala between smokers and controls, and between different smoking states. Furthermore, associations between amygdalar metabolite levels and smoking characteristics were explored. A novel non-water-suppressed proton magnetic resonance spectroscopy protocol was applied to quantify neurometabolites in 28 male smokers (≥15 cigarettes/day) and 21 non-smoking controls, matched in age, education, verbal IQ, and weekly alcohol consumption. Controls were measured once (baseline) and smokers were measured in a baseline state (1-3 h abstinence), during withdrawal (24 h abstinence) and in a satiation state (directly after smoking). Baseline spectroscopy data were compared between groups by independent t-tests or Mann-Whitney-U tests. Smoking state differences were investigated by repeated-measures analyses of variance (ANOVAs). Associations between spectroscopy data and smoking characteristics were explored using Spearman correlations. Good spectral quality, high anatomical specificity (98% mean gray matter) and reliable quantification of most metabolites of interest were achieved in the amygdala. Metabolite levels did not differ between groups, but smokers showed significantly higher glutamine levels at baseline than satiation. Glx levels were negatively associated with pack-years and smoking duration. In summary, this study provides first insights into the neurometabolic profile of the amygdala in smokers with high anatomical specificity. By applying proton magnetic resonance spectroscopy, neurometabolites in smokers during different smoking states and non-smoking controls were quantified reliably. A significant shift in glutamine levels between smoking states was detected, with lower concentrations in satiation than baseline. The negative association between Glx levels and smoking quantity and duration may imply altered glutamate homeostasis with more severe nicotine addiction.

Accumbal-thalamic connectivity and associated glutamate alterations in human cocaine craving: A state-dependent rs-fMRI and 1H-MRS study.

Craving is a core symptom of cocaine use disorder and a major factor for relapse risk. To date, there is no pharmacological therapy to treat this disease or at least to alleviate cocaine craving as a core symptom. In animal models, impaired prefrontal-striatal signalling leading to altered glutamate release in the nucleus accumbens appear to be the prerequisite for cocaine-seeking. Thus, those network and metabolic changes may constitute the underlying mechanisms for cocaine craving and provide a potential treatment target. In humans, there is recent evidence for corresponding glutamatergic alterations in the nucleus accumbens, however, the underlying network disturbances that lead to this glutamate imbalance remain unknown. In this state-dependent randomized, placebo-controlled, double-blinded, cross-over multimodal study, resting state functional magnetic resonance imaging in combination with small-voxel proton magnetic resonance spectroscopy (voxel size: 9.4 × 18.8 × 8.4 mm3) was applied to assess network-level and associated neurometabolic changes during a non-craving and a craving state, induced by a custom-made cocaine-cue film, in 18 individuals with cocaine use disorder and 23 healthy individuals. Additionally, we assessed the potential impact of a short-term challenge of N-acetylcysteine, known to normalize disturbed glutamate homeostasis and to thereby reduce cocaine-seeking in animal models of addiction, compared to a placebo. We found increased functional connectivity between the nucleus accumbens and the dorsolateral prefrontal cortex during the cue-induced craving state. However, those changes were not linked to alterations in accumbal glutamate levels. Whereas we additionally found increased functional connectivity between the nucleus accumbens and a midline part of the thalamus during the cue-induced craving state. Furthermore, obsessive thinking about cocaine and the actual intensity of cocaine use were predictive of cue-induced functional connectivity changes between the nucleus accumbens and the thalamus. Finally, the increase in accumbal-thalamic connectivity was also coupled with craving-related glutamate rise in the nucleus accumbens. Yet, N-acetylcysteine had no impact on craving-related changes in functional connectivity. Together, these results suggest that connectivity changes within the fronto-accumbal-thalamic loop, in conjunction with impaired glutamatergic transmission, underlie cocaine craving and related clinical symptoms, pinpointing the thalamus as a crucial hub for cocaine craving in humans.

Effects of Psychotherapy on Glutamatergic Neurotransmission.

INTRODUCTION: Psychodynamic psychotherapy is an effective and widely used treatment for major depressive disorder (MDD); however, little is known about neurobiological changes associated with induced symptom improvement. METHODS: Proton magnetic resonance spectroscopy with a two-dimensional J-resolved sequence served to test the relationship between glutamate (Glu) and glutamine (Gln) levels, measured separately in pregenual anterior cingulate cortex (pgACC) and the anterior midcingulate cortex (aMCC) as a control region, with change in depression symptoms after 6 months of weekly psychodynamic psychotherapy sessions in MDD patients. Depressed (N = 45) and healthy (N = 30) subjects participated in a baseline proton magnetic resonance spectroscopy measurement and a subgroup of MDD subjects (N = 21) then received once-a-week psychodynamic psychotherapy and participated in a second proton magnetic resonance spectroscopy measurement after 6 months. Change in depression symptoms was assessed using the Hamilton Depression Rating Scale (HAMD). RESULTS: Higher pretreatment pgACC Gln concentrations in MDD patients compared to healthy controls were associated with symptom severity. Patients and controls did not differ regarding Gln levels in aMCC nor regarding Glu levels in both regions. The association of pgACC Gln concentration and severity of depressive symptoms was reversed after 6 months of psychotherapy in MDD subjects. Regarding Gln in aMCC as well as Glu in both regions, there were no significant associations with improvement of depressive symptoms in the course of psychotherapy. DISCUSSION: Findings indicate specific regional effects of psychodynamic psychotherapy on glutamatergic neurotransmission and thereby highlight the key role of the pgACC in both depression pathophysiology and recovery.

Ballistic study on the penetration potential and injury potential of different bullet types in the use of a newly developed bullet shooting stunner for adequate stunning of heavy cattle.

Introduction: Recently, a special bullet shooting stunner for heavy cattle has been developed that fires a bullet instead of a bolt. In the search for a suitable ammunition, the following criteria must be met: First, the energy of the bullet must be sufficient to penetrate the thick frontal bones of heavy cattle. Second, the injury potential at the corresponding penetration depth should preferably be large in order to damage brain tissue relevant to stunning. Third, the bullet must not perforate the occipital bone (over-penetration). Methods: Four different bullet types [Hornady FTX, Hydra-Shok, Black Mamba, and a common full metal jacket (FMJ) bullet] were evaluated in a series of experiments on soap blocks and removed bone plates followed by computed tomography examinations. Penetration potential was evaluated in terms of kinetic energy relative to the caliber of the bullet, i.e., mean energy density (ED). Injury potential was evaluated by the mean extent of the cavity volume (e CV ) at the relevant penetration depth of 5.5 to 7.5 cm in the soap block. Results: All four bullet types passed through the frontal bone plate. The ED was 17.50 J/mm2 (Hornady FTX), 17.46 J/mm2 (Hydra-Shok), 13.47 J/mm2 (Black Mamba), and 13.47 J/mm2 (FMJ). The Hornady FTX and the Hydra-Shok each fragmented heavily. The FMJ was excluded after three experiments due to over-penetrations. The e CV was e CV = 3.77 cm2 (Hornady FTX), 2.71 cm2 (Hydra-Shok), and 1.31 cm2 (Black Mamba), with a significant difference (p = 0.006) between the Hornady FTX and the Black Mamba. Discussion: For use in heavy cattle, the Hornady FTX and the Hydra-Shok are recommended due to the larger e CV than the Black Mamba.

Glutathione in the Pons Is Associated With Clinical Status Improvements in Subacute Spinal Cord Injury.

OBJECTIVES: In spinal cord injury (SCI), the primary mechanical injury is followed by secondary sequelae that develop over the subsequent months and manifests in biochemical, functional, and microstructural alterations, at the site of direct injury but also in the spinal cord tissue above and below the actual lesion site. Noninvasive magnetic resonance spectroscopy (MRS) can be used to assess biochemical modulation occurring in the secondary injury phase, in addition to and supporting conventional MRI, and might help predict and improve patient outcome. In this article, we aimed to examine the metabolic levels in the pons of subacute SCI by means of in vivo proton MRS at 3 T and explore the association to clinical scores. MATERIALS AND METHODS: In this prospective study, between November 2015 and February 2018, single-voxel short-echo MRS data were acquired in healthy controls and in SCI subjects in the pons once during rehabilitation. Besides the single-point MRS examination, in addition, in participants with SCI, the clinical status (ie, motor, light touch, and pinprick scores) was assessed twice: (1) around the MRS session (approximately 10 weeks postinjury) and (2) before discharge (at approximately 9 months postinjury). The group differences were assessed with Kruskal-Wallis test, the post hoc comparison was assessed with Wilcoxon rank sum test, and the clinical correlations were conducted with Spearman rank correlation test. Bayes factor calculations completed the statistical part providing relevant evidence values. RESULTS: Twenty healthy controls (median age, 50 years; interquartile range, 41-55 years; 18 men) and 18 subjects with traumatic SCI (median age, 50 years; interquartile range, 32-58 years; 16 men) are included. Group comparison showed an increase of total N -acetylaspartate and combined glutamate and glutamine levels in complete SCI and a reduction of total creatine in incomplete paraplegic SCI. The proton MRS-based glutathione levels at baseline correlate to the motor score improvement during rehabilitation in incomplete subacute SCI. CONCLUSIONS: This exploratory study showed an association of the metabolite concentration of glutathione in the pons assessed at approximately 10 weeks after injury with the improvements of the motor score during the rehabilitation. Pontine glutathione levels in subjects with traumatic subacute incomplete SCI acquired remote from the injury site correlate to clinical score and might therefore be beneficial in the rehabilitation assessments.

Neurometabolic alterations in the nucleus accumbens of smokers assessed with 1 H magnetic resonance spectroscopy: The role of glutamate and neuroinflammation.

Tobacco use is one of the leading causes of premature death and morbidity worldwide. For smokers trying to quit, relapse rates are high, even after prolonged periods of abstinence. Recent findings in animal models highlight the role of alterations in glutamatergic projections from the prefrontal cortex onto the nucleus accumbens (NAc) in relapse vulnerability. Moreover, inflammatory responses in the NAc have been reported during withdrawal. A novel proton magnetic resonance spectroscopy (1 H-MRS) protocol was applied in humans to measure molar concentrations for glutamate, its sum with glutamine (Glx), and myoinositol plus glycine (mI + Gly) in the NAc (19 smokers, 20 matched controls). Smokers were measured at baseline and during withdrawal and satiation. No difference between groups or smoking states was found for glutamate or Glx, but, in smokers, stronger craving and more severe nicotine dependence were associated with lower baseline glutamate and Glx levels, respectively. Interestingly, mI + Gly concentrations were higher during withdrawal than baseline and correlated negatively with nicotine dependence severity and pack years of smoking. The lack of glutamatergic changes between groups and smoking states may imply that glutamate homeostasis is not significantly altered in smokers or that changes are too small for detection by 1 H-MRS. Moreover, the observed increase in mI + Gly may imply that neuroinflammatory processes occur in the NAc during nicotine withdrawal. These findings shed light on neurobiological relapse mechanisms in smokers and may provide the opportunity to develop more effective treatment options targeting the glutamate and neuroinflammation system.

Fluctuation of Clinical Signs With Near-Syncopal Episodes in a Dog With Gliomatosis Cerebri: A Diagnostic Challenge.

A 2-year-old Bull Mastiff cross Boxer neutered male dog was evaluated because of 2-month history of non-progressive right head tilt and mild vestibular ataxia. MRI of the brain revealed a faint T2W, FLAIR, DWI and ADC heterogenous hyperintense and T1W isointense intra-axial lesion with indistinct margins at the level of the pons and medulla oblongata. The lesion did not show any susceptibility artefact on T2* GRE images or contrast enhancement and CSF analysis was normal. Analysis of the spectra from MRS of the thalamus not promptly available at the time of the MRI study revealed a decreased level of NAA, as seen in people with gliomatosis cerebri. The dog represented 3 weeks later and, on this occasion, displayed left-sided head tilt, left-sided postural reaction deficits and near-syncopal episodes associated with state of confusion. Repeated MRI revealed a larger non-enhancing intra-axial lesion with a more hyperintense signal than previously described. CSF was normal and PCR of CSF for infectious diseases was negative. Thoracic and abdominal computed tomography did not reveal any primary or metastatic process. Immunosuppressive treatment was attempted and the dog remained stable over 5 days, then developed generalized tonic-clonic seizures which led to status epilepticus and death. Histopathology supported the diagnosis of gliomatosis cerebri. Gliomatosis cerebri remains difficult to diagnose ante-mortem, due to the broad age of onset and the variable duration and wide range of clinical signs. The mismatch between MRI findings and clinical presentation, the fluctuating clinical signs with near-syncopal episodes associated with a state of confusion, the presence of an infiltrative brain disease as depicted on MR imaging and a normal CSF analysis, should prompt the clinician to consider possible diagnosis of a widespread infiltrative neoplasm. Although, MRS may help narrow the differential diagnosis in favor of a neoplastic lesion, the overall prognosis remains poor.

7-T MRI for brain virtual autopsy: a proof of concept in comparison to 3-T MRI and CT.

The detection and assessment of cerebral lesions and traumatic brain injuries are of particular interest in forensic investigations in order to differentiate between natural and traumatic deaths and to reconstruct the course of events in case of traumatic deaths. For this purpose, computed tomography (CT) and magnetic resonance imaging (MRI) are applied to supplement autopsy (traumatic death) or to supplant autopsy (natural deaths). This approach is termed "virtual autopsy." The value of this approach increases as more microlesions and traumatic brain injuries are detected and assessed. Focusing on these findings, this article describes the examination of two decedents using CT, 3-T, and 7-T MRI. The main question asked was whether there is a benefit in using 7-T over 3-T MRI. To answer this question, the 3-T and 7-T images were graded regarding the detectability and the assessability of coup/contrecoup injuries and microlesions using 3-point Likert scales. While CT missed these findings, they were detectable on 3-T and 7-T MRI. However, the 3-T images appeared blurry in direct comparison with the 7-T images; thus, the detectability and assessability of small findings were hampered on 3-T MRI. The potential benefit of 7-T over 3-T MRI is discussed.

Impaired glutamate homeostasis in the nucleus accumbens in human cocaine addiction.

Cocaine addiction is characterized by overwhelming craving for the substance, which drives its escalating use despite adverse consequences. Animal models suggest a disrupted glutamate homeostasis in the nucleus accumbens to underlie addiction-like behavior. After chronic administration of cocaine, rodents show decreased levels of accumbal glutamate, whereas drug-seeking reinstatement is associated with enhanced glutamatergic transmission. However, due to technical obstacles, the role of disturbed glutamate homeostasis for cocaine addiction in humans remains only partially understood, and accordingly, no approved pharmacotherapy exists. Here, we applied a tailored proton magnetic resonance spectroscopy protocol that allows glutamate quantification within the human nucleus accumbens. We found significantly reduced basal glutamate concentrations in the nucleus accumbens in cocaine-addicted (N = 26) compared with healthy individuals (N = 30), and increased glutamate levels during cue-induced craving in cocaine-addicted individuals compared with baseline. These glutamatergic alterations, however, could not be significantly modulated by a short-term challenge of N-acetylcysteine (2400 mg/day on 2 days). Taken together, our findings reveal a disturbed accumbal glutamate homeostasis as a key neurometabolic feature of cocaine addiction also in humans. Therefore, we suggest the glutamatergic system as a promising target for the development of novel pharmacotherapies, and in addition, as a potential biomarker for a personalized medicine approach in addiction.

Feasibility, technique and accuracy of ultrasound-guided transurethral injections into the urinary sphincter of female cadavers: proof of concept.

BACKGROUND: The injection of muscle precursor cells (MPC) into the external urinary sphincter muscle (EUS) is a promising therapeutic option for regenerative treatment of stress urinary incontinence (SUI). The objective of the present project was to conduct a pre-clinical trial to investigate the feasibility and accuracy of ultrasound (US) guided, transurethral injections into the EUS of female cadavers. METHODS: This is a prospective, anatomical, interventional and radiological cadaveric laboratory investigation. Two urologists performed transurethral US-guided injections to deliver nano-iron particles into the EUS. The intervention was performed in three unfixed, fresh female cadavers. Each cadaver received MRI before and CT as well as MRI of the pelvis after the injections. RESULTS: The precision and accumulation of nano-iron particles in the EUS was compared using a rating scale to evaluate left versus right and anterior versus posterior distribution in axial and sagittal orientation with US, MRI and CT. The accuracy of our US-guided injections into the anterior target region yielded 4 points on the rating scale. Adequate precision and accumulation of particles in the left versus right EUS were also demonstrated (3 vs. 3.33 points, respectively). Signal intensity in MRI revealed a mean ratio of 0.33 before and after injection. CT scans showed no relevant artefacts impairing the assessment. CONCLUSION: US-guided, transurethral injection into the EUS is feasible and imaging reveals a precise accumulation in the target region. Our method provides an appropriate approach to deliver MPC in the EUS muscle for a regenerative treatment of SUI in the near future.

Noninvasive 7 tesla MRI of fatal craniocerebral gunshots - a glance into the future of radiologic wound ballistics.

Compared to computed tomography (CT), magnetic resonance imaging (MRI) provides superior visualization of the soft tissue. Recently, the first 7 Tesla (7 T) MRI scanner was approved for clinical use, which will facilitate access to these ultra-high-field MRI scanners for noninvasive examinations and scientific studies on decedents. 7 T MRI has the potential to provide a higher signal-to-noise ratio (SNR), a characteristic that can be directly exploited to improve image quality and invest in attempts to increase resolution. Therefore, evaluating the diagnostic potential of 7 T MRI for forensic purposes, such as assessments of fatal gunshot wounds, was deemed essential. In this article, we present radiologic findings obtained for craniocerebral gunshot wounds in three decedents. The decedents were submitted to MRI examinations using a 7 T MRI scanner that has been approved for clinical use and a clinical 3 T MRI scanner for comparison. We focused on detecting tiny injuries beyond the wound tract caused by temporary cavitation, such as microbleeds. Additionally, 7 T T2-weighted MRI highlighted a dark (hypo intense) zone beyond the permanent wound tract, which was attributed to increased amounts of paramagnetic blood components in damaged tissue. Microbleeds were also detected adjacent to the wound tract in the white matter on 7 T MRI. Based on the findings of radiologic assessments, the advantages and disadvantages of postmortem 7 T MRI compared to 3 T MRI are discussed with regard to investigations of craniocerebral gunshot wounds as well as the potential role of 7 T MRI in the future of forensic science.

Heavy metal in radiology: how to reliably differentiate between lodged copper and lead bullets using CT numbers.

BACKGROUND: The in situ classification of bullets is of interest in forensic investigations when the bullet cannot be removed. Although computed tomography (CT) is usually performed on shooting victims, visual assessment, or caliber measurements using CT can be challenging or infeasible if the bullets are deformed or fragmented. Independent from the bullet's intactness, x-ray attenuation values (CT numbers) may provide information regarding the material of the bullet. METHODS: Ethical approval was not required (animal cadavers) or waived by the ethics committee (decedents). Copper and lead bullets were fired into animal cadavers, which then underwent CT scanning at four energy levels (80, 100, 120, and 140 kVp). CT numbers were measured within regions of interest (ROIs). In addition to comparing CT numbers, the dual-energy index (DEI), representing the ratio between the CT numbers of two energy levels, was calculated. The most appropriate method was applied for decedents with fatal gunshot wounds. RESULTS: CT numbers demonstrated no significant difference between copper and lead bullets, and false classifications can easily occur. DEI calculations revealed significant differences between the two groups of bullets. The 120/140 DEIs calculated from the maximum CT numbers obtained from ROIs at the edge of copper versus lead bullets presented a significant difference (p = 0.002) and a gap between the CT numbers of copper and lead bullets and was successfully applied for the decedents. CONCLUSIONS: This study presents a viable method for distinguishing copper and lead bullets in situ via CT and highlights the potential pitfalls of incorrect classifications.

In situ identification of Action 4, SECA and QD-PEP bullets from special police ammunitions by computed tomography.

INTRODUCTION: Special deformation bullets were developed for police forces to achieve a defined penetration depth (avoiding over-penetration) and a controlled energy transfer (avoiding collateral damage). This article focuses on Action 4, SECA and QD-PEP bullets. These 9 mm bullets were specially designed for controlled deformation. The characteristic slight mushrooming with a front cross-section of approximately 11.5 mm after entering a ballistic simulant was verified in ballistic tests. To achieve such slight mushrooming, the projectile's core is hollowed. The purpose of this study was to investigate the feasibility of visualising the hollowed cores of Action 4, SECA and QD-PEP bullets using a standard clinical computed tomography (CT) scanner for non-invasive identification of these special bullets from police ammunitions. METHODS: First, undeformed specimens were scanned to reveal the shape of the hollowed core of each type of special bullet. Second, Action 4, SECA and QD-PEP bullets were fired towards animal cadaver models to visualise their hollow core after deformation inside biological tissue. Third, two reviewers were tasked with identifying special bullets from police ammunition (Action 4 bullets: n = 3) among 10 CT examinations of humans with lodged projectiles who were selected by the supervisor of the study. RESULTS: The CT scans of the undeformed specimens revealed the special design of the bullets' metal core. All special bullets from police ammunitions that were fired towards an animal cadaver model demonstrated the characteristic slight mushrooming. In accordance with the CT scans of the undeformed bullets, visualisation of the individual internal cavities of the special bullets allowed the Action 4, SECA and QD-PEP bullets to be clearly distinguished. With regard to the real forensic cases, both reviewers clearly identified each of the three Action 4 bullets among all other lodged projectiles. CONCLUSIONS: This study demonstrates the feasibility of identifying Action 4, SECA and QD-PEP bullets from special police ammunitions by CT. The individual shapes of the cavity inside the bullets were clearly visible on CT. In situ identification of these bullets can aid in the assessment of injuries, and since these bullets are fabricated from non-ferromagnetic metals, their clear identification allows for magnetic resonance imaging (MRI) without the risk of bullet movement inside the body due to the magnetic pull of the MRI unit. Furthermore, this approach could be of great interest to forensic investigators if patients who received gunshot wounds underwent non-operative treatments and the projectile remains in the body. Since the use of CT is also increasing for medico-legal post-mortem examinations, the identification of lodged projectiles is of interest for a virtual autopsy or 'Virtopsy'.

Visualization and material-based differentiation of lodged projectiles by extended CT scale and the dual-energy index.

Computed tomography (CT) scans of gunshot wounds and their high sensitivity in detecting osseous lesions has often been reported in the literature. However, studies concerning in situ examinations of lodged projectiles with CT to determine the ammunition used are lacking. Projectile visualizations are hampered in standard CT due to the presence of metal artifacts and the limited range of Hounsfield units (HU). The use of special reconstruction algorithms can overcome these limitations. For instance, using extended CT scale (ECTS) reconstruction supports detailed visualizations of metallic objects. In addition to projectile visualizations, X-ray attenuation measurements (CT numbers) of metallic objects can be used to differentiate materials in CT. This study uses real forensic cases to demonstrate that-depending on the degree of deformation-a detailed visualization of lodged projectiles using ECTS can provide useful information regarding the ammunition used and allows accurate caliber measurements. Independent from the degree of deformation, the in situ classification of bullets, even fragmented bullets, according to their metallic components is feasible by dual-energy index (DEI) calculations. The assessment of a lodged projectile with CT images provides useful information on the case; thus, a close examination of lodged projectiles or bullet fragments should be a part of the overall radiological examination for cases of penetrating gunshot wounds.

Comparison of the beta-hydroxybutyrate, glucose, and lactate concentrations derived from postmortem proton magnetic resonance spectroscopy and biochemical analysis for the diagnosis of fatal metabolic disorders.

PURPOSE: The detection and quantification of metabolites relevant for the diagnosis of fatal metabolic disorders by proton magnetic resonance spectroscopy (1H-MRS) was recently demonstrated. This prospective study aimed to compare the concentrations of beta-hydroxybutyrate (BHB), glucose (GLC), and lactate (LAC) derived from both biochemical analyses and 1H-MRS for the diagnosis of fatal metabolic disorders. METHODS: In total, 20 cases with suspected fatal metabolic disorders were included in the study. For the agreement based on thresholds, the concentrations of BHB and GLC in the vitreous humor (VH) from the right vitreous and in cerebrospinal fluid (CSF) from the right lateral ventricle were derived from 1H-MRS and biochemical analyses. The predefined thresholds for pathological elevations were 2.5 mmol/l for BHB and 10 mmol/l for GLC based on the literature. In addition, concentrations of the same metabolites in white matter (WM) tissue from the corona radiata of the right hemisphere were analyzed experimentally using both methods. To enable the biochemical analysis, a dialysate of WM tissue was produced. For all three regions, the LAC concentration was determined by both methods. RESULTS: The conclusive agreement based on thresholds was almost perfect between both methods with only one disagreement in a total of 70 comparisons due to the interference of a ferromagnetic dental brace. The differences in the concentrations between both methods showed high standard deviations. Confidence intervals of the bias not including 0 were found in CSF-GLC (- 3.1 mmol/l), WM-GLC (1.1 mmol/l), and WM-LAC (- 6.5 mmol/l). CONCLUSION: Despite a considerable total error attributable to both methods, MRS derives the same forensic conclusions as conventional biochemical analyses. An adaptation of the protocol to reduce the detected errors and more data are needed for the long-term validation of MRS for the diagnosis of fatal metabolic disorders. The production of WM dialysates cannot be recommended due to high glycolytic loss.

Noninvasive analysis and identification of an intramuscular fluid collection by postmortem 1H-MRS in a case of a fatal motor vehicle accident.

In a case of a fatal traffic accident, a suspicious finding was identified in the muscular tissue of the left thigh by whole-body postmortem computed tomography. To better interpret the finding, the lower extremities were investigated by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS). MRI revealed the presence of an evenly distributed intramuscular fluid and 1H-MRS of a volume within the fluid detected concentrations of acetate and lactate. The fluid was assumed to be an extravasation of an intraosseous infusion, erroneously administered to the intermediate vastus of the left thigh during resuscitation, which was later confirmed when access to resuscitation protocols was granted. Further ex situ 1H-MRS investigations of five different infusion fluids showed the possible discrimination of the fluids and further indicated the unknown fluid to be a Ringer's acetate solution. This paper presents the case-based application of postmortem intramuscular 1H-MRS and introduces the possibility of its use to differentiate exo- and endogenic fluids for forensic interpretation. Further research for this method regarding problems in forensic pathology is needed.

Noninvasive in situ proton MRS in muscle tissue and bone marrow as a novel approach to identify previous freezing in a completely thawed cadaver.

The temporary or permanent storage of human bodies in freezers following a homicide is a documented method for criminal disposal of human corpses. In these cases, the detection of characteristics which indicate that a thawed cadaver or body part was previously frozen provides crucial information for forensic casework. Previous histological and radiological approaches to detect characteristics of previous freezing are based on the formation of bubble-like gas patterns, which are difficult to distinguish from common postmortem gas formation in the course of decomposition. The objective of this study was to detect changes in the muscle tissue and in the bone marrow after freezing and thawing by means of in situ proton magnetic resonance spectroscopy (1 H-MRS) to provide a noninvasive approach to detect postfreezing alterations in human cadavers. In this experimental study, the hind legs of seven sheep were used as substitutes for human tissue. One hind leg underwent 1 H-MRS before and daily after storage in a deep freezer (-20°C) and complete thawing at room temperature (study group: n = 7). The opposite hind leg was kept at room temperature and was measured daily (control group: n = 7). Spectra and relaxation times were measured using single voxel measurements in the muscle tissue and in the bone marrow. 1 H-MRS revealed several changes in the muscle tissue and in the bone marrow after freezing and thawing. A strongly reduced peak area ratio (<20) between bulk methylene and olefinic and glycerol methine and a reduced T2 relaxation time for bulk methylene (<45 ms) measured in the bone marrow were found to be indicators that a sheep leg was previously frozen and thawed independent of the postmortem interval. Noninvasive in situ 1 H-MRS in the bone marrow potentially provides a new method for detecting previous freezing or extreme cooling in cadavers.

Synergy of CT and MRI in detecting trajectories of lodged bullets in decedents and potential hazards concerning the heating and movement of bullets during MRI.

The purpose of this study was to assess the value of magnetic resonance imaging (MRI) in addition to computed tomography (CT) in gunshot wound cases with bullets or pellets lodged inside the head. In this context, the potential heating and movement of the lodged bullets were additionally investigated using animal models. Eleven forensic cases of penetrating gunshot wounds underwent CT and MRI. The data of each imaging modality were reviewed according to the following relevant characteristics: bony lesion at the entrance, intracranial bone fragments, intracranial metal fragments, gunshot residues, the wound channel and the severity of metal artifacts. Four-point Likert scales were used for the assessment. The heating of projectiles and their magnetic field interactions with the static magnetic field were assessed using animal models. MRI presented major advantages in cases with transversal trajectories and non-ferromagnetic bullets compared to CT. In general, MRI enabled a clear visualization of the wound channel and gunshot-related soft tissue injuries. An image fusion of CT and MRI datasets demonstrated the individual strengths of both modalities. Radio frequency (RF)-induced heating due to bullets lodged inside the brain tissue was invalidated. The likelihood of ferromagnetic projectile migration inside brain tissue is low. MRI of decedents with a bullet lodged inside their heads is viable and provides a valuable supplement to CT. The in situ, noninvasive depiction of the wound channel and gunshot-related soft tissue injuries on MRI can contribute to the knowledge of wound ballistics.

Dynamic Metabolic Changes in the Human Thalamus at the Transition From Waking to Sleep - Insights From Simultaneous Functional MR Spectroscopy and Polysomnography.

An important contribution of the thalamus to the transition from wakefulness to sleep is a consistent finding in animal studies. In humans, only little is currently known about the specific role of the thalamus in regulating wake-sleep transitions. Although changes in thalamic blood flow and activity have been reported, the underlying molecular mechanisms have not been investigated. Knowledge about neurotransmitter changes at the wake-to-sleep transition would be indispensable for a better translation of basic animal research findings to humans. Here, we start to fill this important scientific gap. More specifically, we benefit from recent advances in magnetic resonance (MR) spectroscopy, which allow for the non-invasive, local-specific and high-quality detection of naturally occurring metabolite changes in the human brain. We demonstrate in nine young adults able to produce consolidated sleep in the MR spectroscopy scanner, a specific decrease in thalamic glutamate concentration from wakefulness to stage N2 sleep. The magnitude of this decrease was highly correlated with individual N2 sleep duration. When five participants of the original experiment were kept awake in a separate control condition, no decrease in thalamic glutamate levels occurred. The study highlights for the first time in humans that dynamic changes in distinct brain metabolites can be reliably detected at the transition from waking to sleep. The reported methodology to simultaneously acquire functional MR spectroscopy data and neurophysiological signals offers great potential for investigating the molecular mechanisms underlying the transition between and the maintenance of sleep and wake states in humans.