Postmortem imaging: real or virtual?

Since the earliest years after the discovery of X-rays, radiological images have been used successfully for answering medico-legal and forensic questions. The possibility to evaluate the inside of a body without actually opening it has been appreciated and used in forensic pathology since then. However, the introduction of modern cross-sectional imaging techniques into post-mortem investigations has created controversial discussions among the medico-legal community. Terms like "Virtual Autopsy" and "Necro-Radiology" have led to confusion and controversy concerning the role of radiological techniques in forensic case work. Regardless, the use of those techniques in post-mortem investigations is increasing, especially the one of Muti-Detector Computed Tomography (MDCT). But also other imaging techniques such as Postmortem Angiography and Magnetic Resonance Imaging are increasingly applied. This presentation shall give an overview over the different techniques of postmortem imaging. It will critically explain their advantages and limitations in forensic death investigations compared to conventional autopsy. The role of postmortem imaging shall be discussed in order to distinguish between real state of the art and virtual reality.

Understanding diffusion MR imaging techniques: from scalar diffusion-weighted imaging to diffusion tensor imaging and beyond.

The complex structural organization of the white matter of the brain can be depicted in vivo in great detail with advanced diffusion magnetic resonance (MR) imaging schemes. Diffusion MR imaging techniques are increasingly varied, from the simplest and most commonly used technique-the mapping of apparent diffusion coefficient values-to the more complex, such as diffusion tensor imaging, q-ball imaging, diffusion spectrum imaging, and tractography. The type of structural information obtained differs according to the technique used. To fully understand how diffusion MR imaging works, it is helpful to be familiar with the physical principles of water diffusion in the brain and the conceptual basis of each imaging technique. Knowledge of the technique-specific requirements with regard to hardware and acquisition time, as well as the advantages, limitations, and potential interpretation pitfalls of each technique, is especially useful.

The role of imaging in acute ischemic stroke.

Neuroimaging has expanded beyond its traditional diagnostic role and become a critical tool in the evaluation and management of stroke. The objectives of imaging include prompt accurate diagnosis, treatment triage, prognosis prediction, and secondary preventative precautions. While capitalizing on the latest treatment options and expanding upon the "time is brain" doctrine, the ultimate goal of imaging is to maximize the number of treated patients and improve the outcome of one the most costly and morbid disease. A broad overview of comprehensive multimodal stroke imaging is presented here to affirm its utilization.

Widespread age-related differences in the human brain microstructure revealed by quantitative magnetic resonance imaging.

A pressing need exists to disentangle age-related changes from pathologic neurodegeneration. This study aims to characterize the spatial pattern and age-related differences of biologically relevant measures in vivo over the course of normal aging. Quantitative multiparameter maps that provide neuroimaging biomarkers for myelination and iron levels, parameters sensitive to aging, were acquired from 138 healthy volunteers (age range: 19-75 years). Whole-brain voxel-wise analysis revealed a global pattern of age-related degeneration. Significant demyelination occurred principally in the white matter. The observed age-related differences in myelination were anatomically specific. In line with invasive histologic reports, higher age-related differences were seen in the genu of the corpus callosum than the splenium. Iron levels were significantly increased in the basal ganglia, red nucleus, and extensive cortical regions but decreased along the superior occipitofrontal fascicle and optic radiation. This whole-brain pattern of age-associated microstructural differences in the asymptomatic population provides insight into the neurobiology of aging. The results help build a quantitative baseline from which to examine and draw a dividing line between healthy aging and pathologic neurodegeneration.

In situ fluorescence imaging of glutamate-evoked mitochondrial Na+ responses in astrocytes.

Astrocytes can experience large intracellular Na+ changes following the activation of the Na+-coupled glutamate transport. The present study investigated whether cytosolic Na+ changes are transmitted to mitochondria, which could therefore influence their function and contribute to the overall intracellular Na+ regulation. Mitochondrial Na+ (Na+(mit)) changes were monitored using the Na+-sensitive fluorescent probe CoroNa Red (CR) in intact primary cortical astrocytes, as opposed to the classical isolated mitochondria preparation. The mitochondrial localization and Na+ sensitivity of the dye were first verified and indicated that it can be safely used as a selective Na+(mit) indicator. We found by simultaneously monitoring cytosolic and mitochondrial Na+ using sodium-binding benzofuran isophthalate and CR, respectively, that glutamate-evoked cytosolic Na+ elevations are transmitted to mitochondria. The resting Na+(mit) concentration was estimated at 19.0 +/- 0.8 mM, reaching 30.1 +/- 1.2 mM during 200 microM glutamate application. Blockers of conductances potentially mediating Na+ entry (calcium uniporter, monovalent cation conductances, K+(ATP) channels) were not able to prevent the Na+(mit) response to glutamate. However, Ca2+ and its exchange with Na+ appear to play an important role in mediating mitochondrial Na+ entry as chelating intracellular Ca2+ with BAPTA or inhibiting Na+/Ca2+ exchanger with CGP-37157 diminished the Na+(mit) response. Moreover, intracellular Ca2+ increase achieved by photoactivation of caged Ca2+ also induced a Na+(mit) elevation. Inhibition of mitochondrial Na/H antiporter using ethylisopropyl-amiloride caused a steady increase in Na+(mit) without increasing cytosolic Na+, indicating that Na+ extrusion from mitochondria is mediated by these exchangers. Thus, mitochondria in intact astrocytes are equipped to efficiently sense cellular Na+ signals and to dynamically regulate their Na+ content.

Imagerie des atteintes inflammatoires rachidiennes [Imaging in inflammatory spine diseases]

There is a mean delay of 5 to 8 years between the onset of symptoms and the diagnosis of ankylosing spondylitis. This is due to the fact that radiographic sacroiliitis is delayed. The purpose of an earlier diagnosis is emphasized by the need for better management, the new diagnostic method including magnetic resonance imaging and by the efficacy of anti-TNF therapy. The current criteria are classification but not diagnostic criteria. Their sensitivity is insufficient for an early diagnosis of ankylosing spondylitis. MRI criteria allow to differentiate inflammatory signs from degenerative signs in patients sent for aspecific low back pain. The aims of this article are to illustrate the different stages of the disease from early inflammatory involvement to ankylosis and to discuss the role of imaging in the management of affected patients.

Estimating traveltimes and groundwater flow patterns using 3D time-lapse crosshole ERT imaging of electrical resistivity fluctuations induced by infiltrating river water

The infiltration of river water into aquifers is of high relevance to drinking-water production and is a key driver of biogeochemical processes in the hyporheic and riparian zone, but the distribution and quantification of the infiltrating water are difficult to determine using conventional hydrological methods (e.g., borehole logging and tracer tests). By time-lapse inverting crosshole ERT (electrical resistivity tomography) monitoring data, we imaged groundwater flow patterns driven by river water infiltrating a perialpine gravel aquifer in northeastern Switzerland. This was possible because the electrical resistivity of the infiltrating water changed during rainfall-runoff events. Our time-lapse resistivity models indicated rather complex flow patterns as a result of spatially heterogeneous bank filtration and aquifer heterogeneity. The upper part of the aquifer was most affected by the river infiltrate, and the highest groundwater velocities and possible preferential flow occurred at shallow to intermediate depths. Time series of the reconstructed resistivity models matched groundwater electrical resistivity data recorded on borehole loggers in the upper and middle parts of the aquifer, whereas the resistivity models displayed smaller variations and delayed responses with respect to the logging data. in the lower part. This study demonstrated that crosshole ERT monitoring of natural electrical resistivity variations of river infiltrate could be used to image and quantify 3D bank filtration and aquifer dynamics at a high spatial resolution.

Synthesis of F-18-labeled cyclic-[RGDfK] peptides for PET imaging of angiogenesis

Objectives: αvβ3 integrin is of great interest for tumor targeting because of its high concentration in tumor tissue. It recognizes ligands containing an arginine-glycine-aspartate motif (RGD), and a number of RGD-containing peptides have been developed as PET imaging probes of angiogenesis. We synthesized a series of 18F-labeled cyclic-[RGDfK] peptides for in vivo imaging of αvβ3 expression. Our F-18 labeled prosthetic groups were attached to the αvβ3 ligand via click chemistry, and the reaction conditions (time, temperature, solvent and pH) were optimized by using single modified amino acids.Methods: Seven amino acids were selected considering their different biochemical properties (polarity, total charge, presence of aromatic ring and heteroatom). All the amino acids were modified by the introduction of azido moiety to allow the interaction with alkyne prosthetic groups. Once the conditions of the click chemistry were optimized, the prosthetic groups were also coupled with the cyclic-[RGDfK] exhibiting an azido function. 4- Trimethylammonium-nitrobenzene triflate was used as precursor for the radiosynthesis of the prosthetic groups. The fluorination was carried out with K2CO3/K2.2.2 in CH3CN at 95 oC, and the nitro group was reduced with NaBH4 and Pd/C in MeOH. The resulting 18F-aniline was subsequently coupled to alkynoic acids to yield the final F-18 labeled prosthetic groups. Finally, the prosthetic groups were attached to the peptides via Huisgen's cycloaddition. Figure 1. F-18 labeled αvβ3 ligand.Results: Our new prosthetic groups were successfully clicked to the modified amino acids and to the cyclic- [RGDfK], and the reactions were almost quantitative within 1 to 3.5 h. The pH of the reaction did not influence the reaction kinetic and yield. The four steps of the F-18 labeling were completely automated providing the final products in quantities and yields practical for PET imaging. IC50 values of our ligands for αvβ3 and α5β1 demonstrated a high selectivity of our compounds towards αvβ3, as well as the negligible effect of the prosthetic groups on the affinity of the ligand to its receptor, as confirmed by the prediction of the molecular modeling.Conclusions: We have successfully synthesized novel F-18 labeled prosthetic groups, as well as novel PET imaging probes of αvβ3 expression. The reaction conditions of the Huisgen's cycloaddition were optimized with selected modified amino acids, and subsequently transposed to the cyclic-[RGDfK] peptide. IC50 data demonstrate that our 18F-labeled ligands were selective for αvβ3. In vivo microPET/CT studies in tumor bearing mice are underway.

Forensic imaging: New challenges for radiographers : B-588

Purpose: Cross-sectional imaging techniques have pioneered forensic medicine. The involvement of a radiographer and formation of "forensic radiographers" allows an improvement of the quality of radiological examinations and facilitates the implementation of techniques, such as sample collections, and the performance of post-mortem angiography. Methods and Materials: During a period of three months, five radiographers with clinical experience have undergone a special training in order to learn procedures dedicated to forensic imaging. These procedures involved: I). acquisition of MDCT data, II). sample collection for toxicological or histological analyses by performing CT-guided biopsies and liquid sampling, III). post-mortem angiography and IV). post-processing of all data acquired. To perform the post-mortem angiography, radiographers were in charge of the preparation of the perfusion device and the investigated body. Therefore, cannulas were inserted into the femoral vessels and connected to the machine. For angiography, the radiographers had to synchronize the perfusion with the CT-acquisitions. Results: All five radiographers have acquired new skills to become "forensic radiographers". They were able to perform post-mortem MDCT, sample collection, post-mortem angiography and post-processing of the acquired data all by themselves. Most problems have been observed concerning the preparation of the body for post-mortem angiography. Conclusion: Our experience shows that radiographers are able to perform high quality examinations after a short period of training. Their collaboration is well accepted by the forensic team and regarding the increase of radiological exams in forensic department, it would be nonsense to exclude radiographers from the forensic-radiological team.

Vascular Integrins: Therapeutic and Imaging Targets of Tumor Angiogenesis

Cells, including endothelial cells, continuously sense their surrounding environment and rapidly adapt to changes in order to assure tissues and organs homeostasis. The extracellular matrix (ECM) provides a physical scaffold for cell positioning and represents an instructive interface allowing cells to communicate over short distances. Cell surface receptors of the integrin family emerged through evolution as essential mediators and integrators of ECM-dependent communication. In preclinical studies, pharmacological inhibition of vascular integrins suppressed angiogenesis and inhibited tumor progression. alpha(V)beta(3) and alpha(V)beta(5) were the first integrins targeted to suppress tumor angiogenesis. Subsequently, additional integrins, in particular alpha(1)beta(1), alpha(2)beta(1), alpha(5)beta(1), and alpha(6)beta(4), emerged as potential therapeutic targets. Integrin inhibitors are currently tested in clinical trials for their safety and antiangiogenic/antitumor activity. In this chapter, we review the role of integrins in angiogenesis and present recent advances in the use of integrin antagonists as potential therapeutics in cancer and discuss future perspectives.

Post-mortem cardiac 3-T magnetic resonance imaging: visualization of sudden cardiac death?

OBJECTIVES: This study aimed to investigate post-mortem magnetic resonance imaging (pmMRI) for the assessment of myocardial infarction and hypointensities on post-mortem T2-weighted images as a possible method for visualizing the myocardial origin of arrhythmic sudden cardiac death. BACKGROUND: Sudden cardiac death has challenged clinical and forensic pathologists for decades because verification on post-mortem autopsy is not possible. pmMRI as an autopsy-supporting examination technique has been shown to visualize different stages of myocardial infarction. METHODS: In 136 human forensic corpses, a post-mortem cardiac MR examination was carried out prior to forensic autopsy. Short-axis and horizontal long-axis images were acquired in situ on a 3-T system. RESULTS: In 76 cases, myocardial findings could be documented and correlated to the autopsy findings. Within these 76 study cases, a total of 124 myocardial lesions were detected on pmMRI (chronic: 25; subacute: 16; acute: 30; and peracute: 53). Chronic, subacute, and acute infarction cases correlated excellently to the myocardial findings on autopsy. Peracute infarctions (age range: minutes to approximately 1 h) were not visible on macroscopic autopsy or histological examination. Peracute infarction areas detected on pmMRI could be verified in targeted histological investigations in 62.3% of cases and could be related to a matching coronary finding in 84.9%. A total of 15.1% of peracute lesions on pmMRI lacked a matching coronary finding but presented with severe myocardial hypertrophy or cocaine intoxication facilitating a cardiac death without verifiable coronary stenosis. CONCLUSIONS: 3-T pmMRI visualizes chronic, subacute, and acute myocardial infarction in situ. In peracute infarction as a possible cause of sudden cardiac death, it demonstrates affected myocardial areas not visible on autopsy. pmMRI should be considered as a feasible post-mortem investigation technique for the deceased patient if no consent for a clinical autopsy is obtained.