The effect of crack cocaine addiction and age on the microstructure and morphology of the human striatum and thalamus using shape analysis and fast diffusion kurtosis imaging.

The striatum and thalamus are subcortical structures intimately involved in addiction. The morphology and microstructure of these have been studied in murine models of cocaine addiction (CA), showing an effect of drug use, but also chronological age in morphology. Human studies using non-invasive magnetic resonance imaging (MRI) have shown inconsistencies in volume changes, and have also shown an age effect. In this exploratory study, we used MRI-based volumetric and novel shape analysis, as well as a novel fast diffusion kurtosis imaging sequence to study the morphology and microstructure of striatum and thalamus in crack CA compared to matched healthy controls (HCs), while investigating the effect of age and years of cocaine consumption. We did not find significant differences in volume and mean kurtosis (MKT) between groups. However, we found significant contraction of nucleus accumbens in CA compared to HCs. We also found significant age-related changes in volume and MKT of CA in striatum and thalamus that are different to those seen in normal aging. Interestingly, we found different effects and contributions of age and years of consumption in volume, displacement and MKT changes, suggesting that each measure provides different but complementing information about morphological brain changes, and that not all changes are related to the toxicity or the addiction to the drug. Our findings suggest that the use of finer methods and sequences provides complementing information about morphological and microstructural changes in CA, and that brain alterations in CA are related cocaine use and age differently.

Fast diffusion kurtosis imaging of fibrotic mouse kidneys.

Diffusion kurtosis imaging (DKI) is sensitive to tissue microstructure and may therefore be useful in the diagnosis and monitoring of disease in brain and body organs. Generally, diffusion magnetic resonance imaging (dMRI) in the body is challenging because of the heterogeneous body composition, which can cause image artefacts as a result of chemical shifts and susceptibility differences. In addition, the abdomen possesses physiological factors (e.g. breathing, heartbeat, blood flow) which may severely reduce image quality, especially when echo planar imaging is employed, as is typical in dMRI. Collectively, these challenging measurement conditions impede the use and exploration of DKI in the body. This impediment is further exacerbated by the traditionally large amount of data required for DKI and the low signal-to-noise ratio at the b-values needed to effectively probe the kurtosis regime. Recently introduced fast DKI techniques reduce the challenge of DKI in the body by decreasing the data requirement substantially, so that, for example, triggering and breath-hold techniques may be applied for the entire DKI acquisition without causing unfeasible scan times. One common pathological condition for which body DKI may be of immediate clinical value is kidney fibrosis, which causes progressive changes in organ microstructure. With its sensitivity to microstructure, DKI is an obvious candidate for a non-invasive evaluation method. We present preclinical evidence indicating that the rapidly obtainable tensor-derived mean kurtosis ( W̅) distinguishes moderately fibrotic kidneys from healthy controls. The presence and degree of fibrosis are confirmed by histology, which also indicates fibrosis as the main driver behind the DKI differences observed between groups. We therefore conclude that fast kurtosis is a likely candidate for an MRI-based method for the detection and monitoring of renal fibrosis. We provide protocol recommendations for fast renal DKI in humans based on a b-value optimisation performed using data acquired at 3 T in normal human kidney.

Microcirculatory dysfunction and tissue oxygenation in critical illness.

Severe sepsis is defined by organ failure, often of the kidneys, heart, and brain. It has been proposed that inadequate delivery of oxygen, or insufficient extraction of oxygen in tissue, may explain organ failure. Despite adequate maintenance of systemic oxygen delivery in septic patients, their morbidity and mortality remain high. The assumption that tissue oxygenation can be preserved by maintaining its blood supply follows from physiological models that only apply to tissue with uniformly perfused capillaries. In sepsis, the microcirculation is profoundly disturbed, and the blood supply of individual organs may therefore no longer reflect their access to oxygen. We review how capillary flow patterns affect oxygen extraction efficacy in tissue, and how the regulation of tissue blood flow must be adjusted to meet the metabolic needs of the tissue as capillary flows become disturbed as observed in critical illness. Using the brain, heart, and kidney as examples, we discuss whether disturbed capillary flow patterns might explain the apparent mismatch between organ blood flow and organ function in sepsis. Finally, we discuss diagnostic means of detecting capillary flow disturbance in animal models and in critically ill patients, and address therapeutic strategies that might improve tissue oxygenation by modifying capillary flow patterns.

Mean Diffusional Kurtosis in Patients with Glioma: Initial Results with a Fast Imaging Method in a Clinical Setting.

BACKGROUND AND PURPOSE: Diffusional kurtosis imaging is an MR imaging technique that provides microstructural information in biologic systems. Its application in clinical studies, however, is hampered by long acquisition and postprocessing times. We evaluated a new and fast (2 minutes 46 seconds) diffusional kurtosis imaging method with regard to glioma grading, compared it with conventional diffusional kurtosis imaging, and compared the diagnostic accuracy of fast mean kurtosis (MK') to that of the widely used mean diffusivity. MATERIALS AND METHODS: MK' and mean diffusivity were measured in the contrast-enhancing tumor core, the perifocal hyperintensity (indicated on T2 FLAIR images), and the contralateral normal-appearing white and gray matter of 34 patients (22 with high-grade and 12 with low-grade gliomas). MK' and mean diffusivity in the different tumor grades were compared by using a Wilcoxon rank sum test. Receiver operating characteristic curves and the areas under the curve were calculated to determine the diagnostic accuracy of MK' and mean diffusivity. RESULTS: MK' in the tumor core, but not mean diffusivity, differentiated high-grade from low-grade gliomas, and MK' differentiated glioblastomas from the remaining gliomas with high accuracy (area under the curveMK' = 0.842; PMK' < .001). MK' and mean diffusivity identified glioblastomas in the group of high-grade gliomas with similar significance and accuracy (area under the curveMK' = 0.886; area under the curvemean diffusivity = 0.876; PMK' = .003; Pmean diffusivity = .004). The mean MK' in all tissue types was comparable to that obtained by conventional diffusional kurtosis imaging. CONCLUSIONS: The diffusional kurtosis imaging approach used here is considerably faster than conventional diffusional kurtosis imaging methods but yields comparable results. It can be accommodated in clinical protocols and enables exploration of the role of MK' as a biomarker in determining glioma subtypes or response evaluation.