Postmortem MRI Research Articles

Quantifying patterns of pathology: A characterization of the 3D spatial distribution of tau tangles and amyloid plaques in Alzheimer’s disease using multi‐modal image registration with a scattering transform

AbstractBackgroundVolumetric measures of MRI scans have consistently shown medial temporal lobe (MTL) atrophy in individuals across the spectrum of AD. However, these measures are not considered to be specific for AD, partly because a direct link to tau and amyloid pathology has not been demonstrated (Jack et. al, 2018). To address this limitation, we developed multi‐modal image registration and analysis tools to integrate neuropathological data from 2D histology images with 3D postmortem MRI images in the same brain region, in order to quantify the density of tangles and plaques.MethodsWe imaged tissue excised from the MTL at 0.125 mm resolution with an 11T MR scanner (fig 1a) and manually segmented it into subregions (fig 1b). We sliced the tissue into 10um thick sections, 1mm apart, and digitally imaged them with a light microscope after staining for amyloid (6E10) or tau (PHF‐1) (fig 1c). Locations of tangles and plaques on histology were estimated with a deep convolutional neural network (UNET) trained on a smaller set of annotated data (fig 1d). To align histology images with the MRI images, we first computed scattering transforms of histology to capture high resolution textural information (fig 1e). This was then used to find both optimal spatial and intensity profile transformations between the two imaging modalities (fig 1f). We rigidly aligned MRI images to the Mai Paxinos atlas for interpretability.ResultsWe localized tau tangles and amyloid plaques from histology sections of a person with severe AD, and in corresponding 3D MRI images of the brain tissue from the same individual. We quantified density of particles per region. Initial findings demonstrated the highest amount of tau in the entorhinal cortex, subiculum, and CA1 (fig 2) compared to other subregions in the MTL, consistent with Braak staging. No obvious differential distribution of amyloid was observed.ConclusionOur detailed localization of tangles and plaques in 3D offers the opportunity to study spatial distribution of pathology within brain regions among patients that span the spectrum of disease, which will foster more robust comparison with MRI atrophy, and potentially shed new light on the progression of AD.

Diagnostic value of virtual autopsy using pm-MRI at 3T on malformed second trimester fetuses vs classic autopsy

ObjectiveTo determine the diagnostic value of virtual autopsy using post mortem-MRI (pm-MRI) at 3Tesla (T) compared to classic autopsy for the confirmation of fetal structural anomalies and secondly to establish which cases of termination of pregnancy would benefit mostly from a virtual autopsy.MethodsIn each of 32 fetuses included in the study, 32 anatomical structures were assessed, after termination of pregnancy in the second trimester. All cases were evaluated by prenatal ultrasonography, virtual autopsy and classic autopsy, and then divided into four groups: Cerebral Group, Cardiac Group, Renal Group and Other Group (miscellaneous group). The concordance of virtual autopsy with classic autopsy was calculated overall and for each group and each structural item. Also, the concordance between the two methods was assessed using a diagnostic error score (DgE_score), calculated as the absolute value of the difference between the number of malformations detected by classic autopsy per case (CA score) and the number of malformations detected at virtual autopsy per case (VA score).ResultsOverall virtual autopsy demonstrated a diagnostic sensitivity (Se) compared to classic autopsy of 67.33% [95% CI 57.28–76.33], with a specificity (Sp) of 98.37% [95% CI 97.33–99.09], a positive predictive value (PPV) of 81.93% [95% CI 71.95–89.52], a negative predictive value (NPV) of 96.49% [95% CI 95.11–97.57] achieving a diagnostic accuracy of 95.31% [95% CI 93.83–96.52]. Overall, no statistic significant correlation was demonstrated between DgE_score and the gestational age of the fetuses or between DgE_score and the weight of the fetuses, but a significant correlation was revealed between the virtual autopsy and classic autopsy score. The diagnostic utility of virtual autopsy using pm-MRI at 3 T as compared to classic autopsy for each category of termination of pregnancy revealed in the Cerebral Group a Se of 80.00% [95% CI 28.36–99.49], with a 96.30% [95% CI 81.03–99.91], a PPV of 80.00% [95% CI 35.75–96.64] a NPV of 96.30% [95% CI 81.81–99.34], with a diagnostic accuracy of 93.75% [95% CI 79.19% to 99.23] and a Cohen’s Kappa coefficient of 0.76 [95% CI 0.4494–1.0765]; in the Renal Group a Se and Sp of 100%, but in the Cardiac Group the Se was only 60.00% [95% CI 26.24–87.84], Sp 75% [95% CI 34.91–96.81], the PPV 75.00% [95% CI 44.92–91.69], NPV 60% [95% CI 38.87–77.96], with a diagnostic accuracy of 66.67% [95% CI 40.99–86.66] and a Cohen’s Kappa coefficient of 0.32 [95% CI -0.07–0.76].ConclusionsThe results support virtual autopsy using pm-MRI at 3T as a reliable alternative to classic autopsy for the non-forensic analysis of second trimester fetuses. Analyzing the diagnostic utility of virtual autopsy using pm-MRI at 3 T for the confirmation of prenatal ultrasound findings in second trimester fetuses as compared to classic autopsy, the best results were obtained in the Cerebral and Renal Group. Reserved results were found in the Cardiac Group. Therefore, for the pregnancies with termination of pregnancy for cerebral or renal abnormalities, virtual autopsy by pm-MRI at 3T can be taken into consideration as a first-line investigation to confirm the prenatal findings.

3T MRI signal intensity profiles and thicknesses of transient zones in human fetal brain at mid-gestation.

In this study we compare temporal lobe (TL) signal intensity (SI) profiles, along with the average thicknesses of the transient zones obtained from postmortem MRI (pMRI) scans and corresponding histological slices, to the frontal lobe (FL) SI and zone thicknesses, in normal fetal brains. The purpose was to assess the synchronization of the corticogenetic processes in different brain lobes. Nine postmortem human fetal brains without cerebral pathologies, from 19 to 24 weeks of gestation (GW) were analyzed on T2-weighted 3T pMRI, at the coronal level of the thalamus and basal ganglia. The SI profiles of the transient zones in the TL correlate well spatially and temporally to the signal intensity profile of the FL. During the examined period, in the TL, the intermediate and subventricular zone are about the size of the subplate zone (SP), while the superficial SP demonstrates the highest signal intensity. The correlation of the SI profiles and the distributions of the transient zones in the two brain lobes, indicates a time-aligned histogenesis during this narrow time window. The 3TpMRI enables an assessment of the regularity of lamination patterns in the fetal telencephalic wall, upon comparative evaluation of sizes of the transient developmental zones and the SI profiles of different cortical regions. A knowledge of normal vs. abnormal transient lamination patterns and the SI profiles is a prerequisite for further advancement of the MR diagnostic tools needed for early detection of developmental brain pathologies prenatally, especially mild white matter injuries such as lesions of TL due to prenatal cytomegalovirus infections, or cortical malformations.

Post mortem brain temperature and its influence on quantitative MRI of the brain

ObjectiveMRI temperature sensitivity presents a major issue in in situ post mortem MRI (PMMRI), as the tissue temperatures differ from living persons due to passive cooling of the deceased. This study aims at computing brain temperature effects on the MRI parameters to correct for temperature in PMMRI, laying the foundation for future projects on post mortem validation of in vivo MRI techniques.Materials and methodsBrain MRI parameters were assessed in vivo and in situ post mortem using a 3 T MRI scanner. Post mortem brain temperature was measured in situ transethmoidally. The temperature effect was computed by fitting a linear model to the MRI parameters and the corresponding brain temperature.ResultsLinear positive temperature correlations were observed for T1, T2* and mean diffusivity in all tissue types. A significant negative correlation was observed for T2 in white matter. Fractional anisotropy revealed significant correlations in all gray matter regions except for the thalamus.DiscussionThe linear models will allow to correct for temperature in post mortem MRI. Comparing in vivo to post mortem conditions, the mean diffusivity, in contrast to T1 and T2, revealed additional effects besides temperature, such as cessation of perfusion and active diffusion.

Differential Effect of Iron and Myelin on Susceptibility MRI in the Substantia Nigra.

Background The heterogeneous composition of substantia nigra (SN), including iron, nigrosome-1 substructure, and myelinated white matter, complicates the interpretation of MRI signals. Purpose To investigate R2* and quantitative susceptibility mapping (QSM) in the SN subdivisions of participants with Parkinson disease and healthy control subjects. Materials and Methods In this prospective study conducted from November 2018 to November 2019, participants with Parkinson disease and sex-matched healthy control subjects underwent 3-T MRI. R2* and QSM values were measured and compared in the anterior SN and posterior SN at the rostral (superior) and caudal (inferior) levels. Postmortem MRI and histology correlation of midbrain tissues was evaluated to investigate the effect of myelin and iron in the SN on R2* and QSM values. Results Forty individuals were evaluated: 20 healthy control subjects (mean age, 61 years ± 3 [standard deviation]; 10 men) and 20 participants with Parkinson disease (mean age, 61 years ± 4; 10 men). The R2* values of participants with Parkinson disease were higher in all subdivisions of the SN compared with R2* values in healthy control subjects (all P < .05). For QSM, no evidence of a difference was found in the rostral posterior SN (healthy control subjects, 54.1 ppb ± 21.0; Parkinson disease, 62.2 ppb ± 19.8; P = .49). The combination of rostral R2* and caudal QSM values resulted in an area under the receiver operating characteristic curve of 0.84. R2* values showed higher correlation with QSM values at the caudal level than at the rostral level within each group (all P < .001). Postmortem investigation demonstrated that R2* and QSM values showed weak correlation in the myelin-rich areas (r = 0.22 and r = 0.36, P < .001) and strong correlation in myelin-scanty areas (r ranged from approximately 0.52 to approximately 0.78, P < .001) in the SN. Conclusion Considering the iron and myelin distribution in the substantia nigra subdivisions, the subdivisional analysis of substantia nigra using R2* and quantitative susceptibility mapping might aid in specifically differentiating individuals with Parkinson disease from healthy control subjects. © RSNA, 2021 Online supplemental material is available for this article.

Amyloid-β, p-tau and reactive microglia are pathological correlates of MRI cortical atrophy in Alzheimer's disease.

Alzheimer’s disease is characterized by cortical atrophy on MRI and abnormal depositions of amyloid-beta, phosphorylated-tau and inflammation pathologically. However, the relative contribution of these pathological hallmarks to cortical atrophy, a widely used MRI biomarker in Alzheimer’s disease, is yet to be defined. Therefore, the aim of this study was to identify the histopathological correlates of MRI cortical atrophy in Alzheimer’s disease donors, and its typical amnestic and atypical non-amnestic phenotypes. Nineteen Alzheimer’s disease (of which 10 typical and 9 atypical) and 10 non-neurological control brain donors underwent post-mortem in situ 3T 3D-T1, from which cortical thickness was calculated with Freesurfer. Upon subsequent autopsy, 12 cortical brain regions from the right hemisphere and 9 from the left hemisphere were dissected and immunostained for amyloid-beta, phosphorylated-tau and reactive microglia, and percentage area load was calculated for each marker using ImageJ. In addition, post-mortem MRI was compared to ante-mortem MRI of the same Alzheimer’s disease donors when available. MRI-pathology associations were assessed using linear mixed models. Higher amyloid-beta load weakly correlated with higher cortical thickness globally (r = 0.22, P = 0.022). Phosphorylated-tau strongly correlated with cortical atrophy in temporal and frontal regions (−0.76 < r < −1.00, all P < 0.05). Reactive microglia load strongly correlated with cortical atrophy in the parietal region (r = −0.94, P < 0.001). Moreover, post-mortem MRI scans showed high concordance with ante-mortem scans acquired <1 year before death. In conclusion, distinct histopathological markers differently correlated with cortical atrophy, highlighting their different roles in the neurodegenerative process, and therefore contributing to the understanding of the pathological underpinnings of MRI atrophic patterns in Alzheimer’s disease. In our cohort, no or only subtle differences were found in MRI-pathology associations in Alzheimer’s disease phenotypes, indicating that the histopathological correlates of cortical atrophy in typical and atypical phenotypes might be similar. Moreover, we show that post-mortem in situ MRI can be used as proxy for ante-mortem in vivo MRI.

Reader Response: Early Postmortem Brain MRI Findings in COVID-19 Non-survivors.

Coolen et al.1 published valuable research exploring the existence of structural brain abnormalities by MRI studies in nonsurvivors of COVID-19. They described cortico-subcortical edematous changes suggestive of posterior reversible encephalopathy syndrome (PRES) in 1 decedent. The most accepted theory of PRES is a loss of autoregulation in cerebral blood flow—usually associated with hypertension or arterial pressure fluctuations, with a subsequent increase in vascular permeability and leakage of blood plasma and erythrocytes—producing vasogenic edema. Other theories have been proposed in the pathogenesis of PRES, but they all lead to activation and injury of the endothelium, stimulation of the immune system, and release of cytokines.2,3 SARS-CoV-2 neurotropism has been recently supported.4,5 Its invasion of the CNS is usually responsible of cytokine storms, leading to endothelium dysfunction,1,2 which might trigger the necessary pathophysiology mechanisms for PRES appearance. The patient described by Coolen et al. did not show arterial pressure abnormalities, and then, the direct virus invasion to the brain seems to be the mechanism involved in this patient. PRES pathophysiology is directly related to the posterior circulation of the brain. The posterior cerebral artery also offers blood supply to a large portion of the thalamus and the upper brainstem.1-3 As this is a reversible syndrome, the possibility of the occurrence of endothelial dysfunction in the rest of the brainstem—affecting the respiratory centers—cannot be excluded. I discussed that SARS-CoV-2 infection might partially explain the acute respiratory distress syndrome refractory to treatments, commonly found in this pandemic.5

Reader Response: Early Postmortem Brain MRI Findings in COVID-19 Non-survivors.

I read the article by Coolen et al.1 with interest. The wide range of manifestations of the coronavirus disease 2019 (COVID-19) pandemic is not yet known. In their article, Coolen et al. reported 2 patients presenting with subcortical micro- and macrobleeds, 1 patient with cortico-subcortical edematous changes evocative of PRES, and the last patient presenting with nonspecific deep white matter changes. Multiple neuroradiologic patterns attributable to the coronavirus have been reported.2,3 Recently, various cerebral hemorrhagic disorders have been reported, including both intraparenchymal hemorrhages and diffuse microhemorrhages of the white matter. Extensive and isolated white matter microhemorrhages are found in patients hospitalized in intensive care units for various causes.4 Regarding PRES, it has been suggested that SARS-CoV-2 could act as a triggering factor for the development of rapid autoimmune and/or autoinflammatory dysregulation and lead to the endothelial dysfunction. The neuropathologic findings from the autopsies of 18 patients with COVID-19 infection from a recent article showed only hypoxic changes and did not show encephalitis or other specific brain changes referable to the virus.5 Considering this, the radiologic abnormalities reported by the authors do not appear to be related to encephalitis or vasculitis due to coronavirus but appear to be related to hypoxemia or autoinflammatory dysregulation.

Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-β and α-synuclein pathology were rated on a scale of 0 (absent)—3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman’s rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = − 0.27 to r = − 0.46), and (2) tau with BA35 (r = − 0.31) and SRLM thickness (r = − 0.33). In amyloid-β and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = − 0.40), BA35 (r = − 0.55), subiculum (r = − 0.42) and CA1 thickness (r = − 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-β suggests a role of Primary Age-Related Tauopathy in neurodegeneration.

Fatal methemoglobinemia: A case series highlighting a new trend in intentional sodium nitrite or sodium nitrate ingestion as a method of suicide

Unintentional exposure to nitrite- or nitrate-containing toxic salts is a recognized cause of acquired methemoglobinemia (MetHb). This systemic alteration of the blood can be fatal if not recognized and treated promptly. The intentional ingestion of sodium nitrite (NaNO2) or sodium nitrate (NaNO3), causing MetHb, is an uncommon and recently identified method of suicide, with the first reported case in the literature occurring in New Zealand in 2010. In this case series we present 28 cases of sudden death of individuals with evidence of MetHb and/or toxic salt ingestion, occurring in the Province of Ontario, Canada, between the years 1980 and 2020, inclusive. Of the 28 deaths in our case series, 25 showed evidence of intentional ingestion of sodium nitrite or sodium nitrate salts. Our year-over-year data demonstrated this is an increasingly used method of suicide in our provincial population, with the majority of cases occurring in the final two years of our study.Postmortem detection of MetHb is typically established via screening techniques such as scene evidence suggesting fatal consumption of a toxic salt in addition to the characteristic grey-purple lividity observed upon the body. The diagnosis can be established via postmortem blood testing demonstrating elevated methemoglobin saturation. Additionally, we have confirmed that postmortem MRI in cases of MetHb demonstrates a T1-bright (hyperintense) signal of the blood; both within intracardiac blood on chest MRIs and postmortem blood samples in tubes.

Physical activity, brain tissue microstructure, and cognition in older adults.

ObjectiveTo test whether postmortem MRI captures brain tissue characteristics that mediate the association between physical activity and cognition in older adults.MethodsParticipants (N = 318) were older adults from the Rush Memory and Aging Project who wore a device to quantify physical activity and also underwent detailed cognitive and motor testing. Following death, cerebral hemispheres underwent MRI to quantify the transverse relaxation rate R2, a metric related to tissue microstructure. For analyses, we reduced the dimensionality of the R2 maps from approximately 500,000 voxels to 30 components using spatial independent component analysis (ICA). Via path analysis, we examined whether these R2 components attenuated the association between physical activity and cognition, controlling for motor abilities and indices of common brain pathologies.ResultsTwo of the 30 R2 components were associated with both total daily physical activity and global cognition assessed proximate to death. We visualized these components by highlighting the clusters of voxels whose R2 values contributed most strongly to each. One of these spatial signatures spanned periventricular white matter and hippocampus, while the other encompassed white matter of the occipital lobe. These two R2 components partially mediated the association between physical activity and cognition, accounting for 12.7% of the relationship (p = .01). This mediation remained evident after controlling for motor abilities and neurodegenerative and vascular brain pathologies.ConclusionThe association between physically activity and cognition in older adults is partially accounted for by MRI-based signatures of brain tissue microstructure. Further studies are needed to elucidate the molecular mechanisms underlying this pathway.

Fetal thick corpus callosum: new insights from neuroimaging and neuropathology in two cases and literature review.

To describe the correlation between fetal imaging (in vivo and ex vivo) and neuropathology in two fetuses at early gestational age (GA) with isolated thick corpus callosum (CC), a rare finding whose pathological significance and neuropathology data are scarce. Two fetuses at 21-week GA underwent fetal MRI (fMRI) for suspected callosal anomalies at ultrasound (US). After fMRI results, termination of pregnancy (TOP) was carried out and post-mortem MRI (pmMRI) was performed. Neuropathology correlation consisted in macro and microscopic evaluation with sections prepared for hematoxylin-eosin and immunohistochemistry staining. Fetal imaging confirmed in both cases the presence of a shorter and thicker CC with respect to the reference standard at the same GA, without a clear distinction between its different parts. Moreover, on pmMRI, an abnormal slightly T2-weighted hyperintense layer along the superior and inferior surface of CC was noted in both cases. At histopathology, these findings corresponded to an increased amount of white matter tracts but also to an abnormal representation of embryological structures that contribute to CC development, naming induseum griseum (IG) and the glioepithelial layer (GL) of the "callosal sling." After reviewing the literature data, we confirmed the recent embryological theory regarding the CC development and provide new insights into the pathophysiology of the abnormal cases. An abnormally thick CC at the early fetal period could be associated to an abnormal representation of the midline glia structures, so to result in potential disturbance of the axon guidance mechanism of callosal formation and eventually in CC dysgenesis.

Post-mortem CMR in a model of sudden death due to myocardial ischemia: validation with connexin-43.

We sought to evaluate the effectiveness of post-mortem cardiac magnetic resonance (PM-CMR) for the identification of myocardial ischemia as cause of sudden cardiac death (SCD) when the time interval between the onset of ischemia and SCD is ≤ 90 min. PM-CMR was performed in 8 hearts explanted from pigs with spontaneous death caused by occlusion of the left anterior descending coronary artery: 4 with SCD after ≤ 40 min of coronary occlusion and 4 between 40 and 90 min. PM-CMR included conventional T1 and T2-weighted image and T1, T2, and T2* mapping techniques. Imaging data were compared and validated with immunohistochemical evaluation of the altered proportion and redistribution of phosphorylated versus non-phosphorylated connexin 43 (CX43 and npCX43, respectively), an established molecular marker of myocardial ischemia. At T2-weighted images, the ischemic core was hypointense (core/remote ratio 0.67 ± 0.11) and surrounded by and hyperintense border zone. Compared to remote myocardium, the ischemic core had higher T1 (p = 0.0008), and lower T2 (p = 0.007) and T2* (p = 0.002). Cytoplasmatic npX43 and the npCX43/CX43 ratio were significantly higher in animals deceased > 40 min than in others. PM-CMR can reliably detect early signs of myocardial damage induced by ischemia, based on conventional pulse sequences complemented by a novel ad hoc application of quantitative mapping techniques. • Post-mortem MRI may help to understand cause of sudden cardiac death. • Post-mortem MRI allows detection of signs of myocardial ischemia as cause of sudden cardiac death within 90 and 40 min following coronary occlusion as demonstrated in a pig model of myocardial ischemia. • Signs of myocardial ischemia using conventional and mapping MRI technique are associated with the immunohistochemical changes of phosphorylated and dephosphorylated connexin-43 which is an established molecular marker of myocardial ischemia.

Synchrotron X-ray micro-CT as a validation dataset for diffusion MRI in whole mouse brain.

To introduce synchrotron X-ray microcomputed tomography (microCT) and demonstrate its use as a natively isotropic, nondestructive, 3D validation modality for diffusion MRI in whole, fixed mouse brain. Postmortem diffusion MRI and microCT data were acquired of the same whole mouse brain. Diffusion data were processed using constrained spherical deconvolution. Synchrotron data were acquired at an isotropic voxel size of 1.17 μm. Structure tensor analysis was used to calculate fiber orientation distribution functions from the microCT data. A pipeline was developed to spatially register the 2 datasets in order to perform qualitative comparisons of fiber geometries represented by fiber orientation distribution functions. Fiber orientations from both modalities were used to perform whole-brain deterministic tractography to demonstrate validation of long-range white matter pathways. Fiber orientation distribution functions were able to be extracted throughout the entire microCT dataset, with spatial registration to diffusion MRI simplified due to the whole brain extent of the microCT data. Fiber orientations and tract pathways showed good agreement between modalities. Synchrotron microCT is a potentially valuable new tool for future multi-scale diffusion MRI validation studies, providing comparable value to optical histology validation methods while addressing some key limitations in data acquisition and ease of processing.

Diffuse axonal injury has a characteristic multidimensional MRI signature in the human brain.

Axonal injury is a major contributor to the clinical symptomatology in patients with traumatic brain injury. Conventional neuroradiological tools, such as CT and MRI, are insensitive to diffuse axonal injury (DAI) caused by trauma. Diffusion tensor MRI parameters may change in DAI lesions; however, the nature of these changes is inconsistent. Multidimensional MRI is an emerging approach that combines T1, T2, and diffusion, and replaces voxel-averaged values with distributions, which allows selective isolation of specific potential abnormal components. By performing a combined post-mortem multidimensional MRI and histopathology study, we aimed to investigate T1-T2-diffusion changes linked to DAI and to define their histopathological correlates. Corpora callosa derived from eight subjects who had sustained traumatic brain injury, and three control brain donors underwent post-mortem ex vivo MRI at 7 T. Multidimensional, diffusion tensor, and quantitative T1 and T2 MRI data were acquired and processed. Following MRI acquisition, slices from the same tissue were tested for amyloid precursor protein (APP) immunoreactivity to define DAI severity. A robust image co-registration method was applied to accurately match MRI-derived parameters and histopathology, after which 12 regions of interest per tissue block were selected based on APP density, but blind to MRI. We identified abnormal multidimensional T1-T2, diffusion-T2, and diffusion-T1 components that are strongly associated with DAI and used them to generate axonal injury images. We found that compared to control white matter, mild and severe DAI lesions contained significantly larger abnormal T1-T2 component (P = 0.005 and P < 0.001, respectively), and significantly larger abnormal diffusion-T2 component (P = 0.005 and P < 0.001, respectively). Furthermore, within patients with traumatic brain injury the multidimensional MRI biomarkers differentiated normal-appearing white matter from mild and severe DAI lesions, with significantly larger abnormal T1-T2 and diffusion-T2 components (P = 0.003 and P < 0.001, respectively, for T1-T2; P = 0.022 and P < 0.001, respectively, for diffusion-T2). Conversely, none of the conventional quantitative MRI parameters were able to differentiate lesions and normal-appearing white matter. Lastly, we found that the abnormal T1-T2, diffusion-T1, and diffusion-T2 components and their axonal damage images were strongly correlated with quantitative APP staining (r = 0.876, P < 0.001; r = 0.727, P < 0.001; and r = 0.743, P < 0.001, respectively), while producing negligible intensities in grey matter and in normal-appearing white matter. These results suggest that multidimensional MRI may provide non-invasive biomarkers for detection of DAI, which is the pathological substrate for neurological disorders ranging from concussion to severe traumatic brain injury.

Clinical Application of Postmortem Magnetic Resonance Imaging in Neonates

Background: Recent reports advocate the use of MRI either as a substitute for postmortem examinations or for a more targeted autopsy. Methods: A full-body postmortem MRI (pMRI) of infants was performed as early as possible after death, and findings were compared to clinical premortem diagnoses. Results: Thirty-one infants were scanned during the study period. Median gestation at birth was 34 weeks (ranges: 24–43). In 3 (10%) cases, no new findings were detected. In 2 (6%), new minor findings not related to the cause of death were detected, and in 17 (55%), new minor findings related to the cause of death were detected. New major findings related to the cause of death were detected in 4 (13%) cases, and new major findings not related to the cause of death were detected in 5 (16%) cases. In 3 (10%), findings thought to alter the perceived cause of death were detected. Overall, in 23 (74%) cases, pMRI findings reinforced the clinical premortem diagnoses. Conclusions: pMRI is a culturally accepted alternative when autopsy is not performed and can either reinforce, refute, or add to premortem clinical diagnoses.

Iron distribution in the lentiform nucleus: A post-mortem MRI and histology study.

Iron plays an important role in many neurobiological processes, especially in the basal ganglia, the brain structures with the highest concentration. Composed of the pallidum and putamen, the lentiform nucleus plays a key role in the basal ganglia circuitry. With MRI advances, iron-based sequences such as R2* and quantitative susceptibility mapping (QSM) are now available for detecting and quantifying iron in different brain structures. Since their validation using classic iron detection techniques (histology or physical techniques), these sequences have attracted growing clinical attention, especially in the field of extrapyramidal syndromes that particularly affect the basal nuclei. Accurate mapping of iron in these nuclei and their connections is needed to gain a better understanding of this specific anatomy, before considering its involvement in the physiopathological processes. We performed R2* and QSM along with Perls histology, to gain new insights into the distribution of iron in the lentiform nucleus and its surrounding structures, based on four specimens obtained from voluntary donors. We found that iron is preferentially distributed in the anterior part of the globus pallidus externus and the posterior part of the putamen. The lateral wall of the putamen is iron-poor, compared with the lateral medullary lamina and intraputaminal fibers. The relevance of perivascular iron concentration, along with pallido- and putaminofugal iron-rich fibers, is discussed.

Evaluation of post-mortem high-field MRI at 7T compared to conventional autopsy: a morphometric study

Objective. The aim of our study was to establish if high-field post-mortem MRI at 7T can perform three-dimensional measurements of the fetal heart, and retrieve results comparable to post-mortem macroscopic measurements performed at autopsy, in fetuses with whole body weight below 500 g. Methodology. Twelve second-trimester fetuses with gestational ages ranging from 13 to 19 weeks of gestation were considered. All fetuses resulted from therapeutic termination of pregnancy (TOP) due to plurimalformative syndromes or chromosomal anomalies. All cases were immersed in 10% formalin solution, and after proper fixation they were examined using high-field MRI at 7T. After post-mortem imagistic examination, all cases were submitted to conventional autopsy. Three-axis cardiac measurements were performed by both examination methods, using the same landmarks. Results. We observed a strong correlation between post-mortem MRI measurements at 7T and post-mortem macroscopic measurements at autopsy, with p<0.001. The coefficient of correlation (r) for all three axes was above or equal to 0.90. Bland Altman plots showed overall good agreement between measurements performed by both methods. Conclusions. Using 7T post-mortem MRI for three-dimensional morphometric evaluation of the fetal heart in the second-trimester fetuses with a body weight less than 500 g, the obtained results are comparable to the macroscopic measurements performed during conventional autopsy.

Postmortem MRI Characterization of Cadaveric Hypostases in Deceased Newborns.

Using postmortem MRI, we studied the features of the development of internal cadaveric hypostasis in dead newborns. Postmortem radiological and pathoanatomical examination of 62 bodies of newborns and infants who died at the age of 1.5 h to 49 days was carried out. After the death was ascertained, prior to MRI, the bodies were stored in a refrigerator at 4°C in the supine position. Depending on the duration of the postmortem period (2-72 h), all observations were divided into eight groups. Prior to autopsy, an MRI scan was performed in T1 and T2 standard modes, followed by analysis of the presence and severity of the gradient line of the intensity of the MR signal in the liver and lung tissue in the ventral (overlying) and dorsal (underlying) areas, as well as the presence of a gradient of the intensity of the blood signal in the heart cavity and in the aortic lumen. The main manifestations of cadaveric hypostasis in the liver and lungs are changes of the MR signal intensity in the ventral and dorsal regions with the appearance of a horizontal gradient of the MR signal intensity, which reflects the location of the body after death. In the heart cavity and in the aortic lumen, there is also a gradient of the blood signal intensity of various severity with the visualization of two or three of its layers. The revealed features of the MRI signal intensity and, accordingly, the presence of its horizontal gradient depended not only on the MRI mode of the study, but also on the studied organ and the duration of the postmortem period. This should be taken into account when analyzing the results of virtopsy and determining the links of thanatogenesis of dead newborns and infants.

Technical and methodological support for postmortem radiation examinations in the pathological departments and the forensic bureau

The purpose of the work is to analyze the technical and methodological features of postmortem radiation studies based on literature data and the results of our own experience. To designate such studies, the term thanatoradiology has been proposed. The basis for the effective conduct of a thanatodiological examination is adequate technical support, which equally consists of the capabilities of the equipment for obtaining radiographs, CT and MR tomograms (type and generation of the device, technical features of a particular model), as well as the capabilities of the radiologist's workstation with the help of which the computer processing of the obtained images is carried out, three-dimensional reconstructions are performed, the calculation of planar and volumetric parameters and additional information is obtained. The use of an X-ray unit allows one to assess only pronounced pathology and the presence of foreign objects. The effectiveness of a computed tomography device depends on the choice of the slice thickness and the step of the examination table. Research on a magnetic resonance imager is effective at certain magnetic induction strength, the form of a magnetic coil and the used mode of recording a pulse sequence. The objectivity and efficiency of digital processing of tomograms consists of the type of a radiologist's workstation and installed programs for post-processing tomograms, including for modeling three-dimensional images and color mapping. The choice of a specific method of postmortem radiation research should be determined mainly by the research objectives. Research should be carried out taking into account age, body weight, individual characteristics and the state of body tissues. Today, it is advisable to use radiation methods as part of a comprehensive pathological and anatomical or forensic medical research to improve the quality and shorten the autopsy duration. The development of a unified protocol for postmortem CT and MRI studies that meets the pathological, anatomical and forensic requirements remains an urgent task.