Pseudocontinuous arterial spin labeling reveals dissociable effects of morphine and alcohol on regional cerebral blood flow

We have examined sensitivity and specificity of pseudocontinuous arterial spin labeling (PCASL) to detect global and regional changes in cerebral blood flow (CBF) in response to two different psychoactive drugs. We tested alcohol and morphine in a placebo-controlled, double-blind randomized study in 12 healthy young men. Drugs were administered intravenously. Validated pharmacokinetic protocols achieved minimal intersubject and intrasubject variance in plasma drug concentration. Permutation-based statistical testing of a mixed effect repeated measures model revealed a widespread increase in absolute CBF because of both morphine and alcohol. Conjunction analysis revealed overlapping effects of morphine and alcohol on absolute CBF in the left anterior cingulate, right hippocampus, right insula, and left primary sensorimotor areas. Effects of morphine and alcohol on relative CBF (obtained from z-normalization of absolute CBF maps) were significantly different in the left putamen, left frontoparietal network, cerebellum, and the brainstem. Corroborating previous PET results, our findings suggest that PCASL is a promising tool for central nervous system drug research

Microstructural white matter integrity in relation to vascular reactivity in Dutch-type hereditary cerebral amyloid angiopathy

Cerebral Amyloid Angiopathy (CAA) is characterized by cerebrovascular amyloid-β accumulation leading to hallmark cortical MRI markers, such as vascular reactivity, but white matter is also affected. By studying the relationship in different disease stages of Dutch-type CAA (D-CAA), we tested the relation between vascular reactivity and microstructural white matter integrity loss. In a cross-sectional study in D-CAA, 3 T MRI was performed with Blood-Oxygen-Level-Dependent (BOLD) fMRI upon visual activation to assess vascular reactivity and diffusion tensor imaging to assess microstructural white matter integrity through Peak Width of Skeletonized Mean Diffusivity (PSMD). We assessed the relationship between BOLD parameters - amplitude, time-to-peak (TTP), and time-to-baseline (TTB) - and PSMD, with linear and quadratic regression modeling. In total, 25 participants were included (15/10 pre-symptomatic/symptomatic; mean age 36/59 y). A lowered BOLD amplitude (unstandardized β = 0.64, 95%CI [0.10, 1.18], p = 0.02, Adjusted R2 = 0.48), was quadratically associated with increased PSMD levels. A delayed BOLD response, with prolonged TTP (β = 8.34 × 10-6, 95%CI [1.84 × 10-6, 1.48 × 10-5], p = 0.02, Adj. R2 = 0.25) and TTB (β = 6.57 × 10-6, 95%CI [1.92 × 10-6, 1.12 × 10-5], p = 0.008, Adj. R2 = 0.29), was linearly associated with increased PSMD. In D-CAA subjects, predominantly in the symptomatic stage, impaired cerebrovascular reactivity is related to microstructural white matter integrity loss. Future longitudinal studies are needed to investigate whether this relation is causal.</p

Current Understanding of the Anatomy, Physiology, and Magnetic Resonance Imaging of Neurofluids: Update From the 2022 "ISMRM Imaging Neurofluids Study group" Workshop in Rome

Neurofluids is a term introduced to define all fluids in the brain and spine such as blood, cerebrospinal fluid, and interstitial fluid. Neuroscientists in the past millennium have steadily identified the several different fluid environments in the brain and spine that interact in a synchronized harmonious manner to assure a healthy microenvironment required for optimal neuroglial function. Neuroanatomists and biochemists have provided an incredible wealth of evidence revealing the anatomy of perivascular spaces, meninges and glia and their role in drainage of neuronal waste products. Human studies have been limited due to the restricted availability of noninvasive imaging modalities that can provide a high spatiotemporal depiction of the brain neurofluids. Therefore, animal studies have been key in advancing our knowledge of the temporal and spatial dynamics of fluids, for example, by injecting tracers with different molecular weights. Such studies have sparked interest to identify possible disruptions to neurofluids dynamics in human diseases such as small vessel disease, cerebral amyloid angiopathy, and dementia. However, key differences between rodent and human physiology should be considered when extrapolating these findings to understand the human brain. An increasing armamentarium of noninvasive MRI techniques is being built to identify markers of altered drainage pathways. During the three-day workshop organized by the International Society of Magnetic Resonance in Medicine that was held in Rome in September 2022, several of these concepts were discussed by a distinguished international faculty to lay the basis of what is known and where we still lack evidence. We envision that in the next decade, MRI will allow imaging of the physiology of neurofluid dynamics and drainage pathways in the human brain to identify true pathological processes underlying disease and to discover new avenues for early diagnoses and treatments including drug delivery. Evidence level: 1. Technical Efficacy: Stage 3

MACI - a new era?

Full thickness articular cartilage defects have limited regenerative potential and are a significant source of pain and loss of knee function. Numerous treatment options exist, each with their own advantages and drawbacks. The goal of this review is to provide an overview of the problem of cartilage injury, a brief description of current treatment options and outcomes, and a discussion of the current principles and technique of Matrix-induced Autologous Chondrocyte Implantation (MACI). While early results of MACI have been promising, there is currently insufficient comparative and long-term outcome data to demonstrate superiority of this technique over other methods for cartilage repair

A novel approach to measure local cerebral haematocrit using MRI.

The percentage blood volume occupied by red blood cells is known as haematocrit. While it is straightforward to measure haematocrit in large arteries, it is very challenging to do it in microvasculature (cerebral haematocrit). Currently, this can only be done using invasive methods (e.g. PET), but their use is very limited. Local variations in cerebral haematocrit have been reported in various brain abnormalities (e.g. stroke, tumours). We propose a new approach to image cerebral haematocrit using MRI, which relies on combining data from two measurements: one that provides haematocrit-weighted and other one haematocrit-independent values of the same parameter, thus providing an easily obtainable measurement of this important physiological parameter. Four different implementations are described, with one illustrated as proof-of-concept using data from healthy subjects. Cerebral haematocrit measurements were found to be in general agreement with literature values from invasive techniques (e.g. cerebral/arterial ratios of 0.88 and 0.86 for sub-cortical and cortical regions), and showed good test-retest reproducibility (e.g. coefficient-of-variation: 15% and 13% for those regions). The method was also able to detect statistically significant haematocrit gender differences in cortical regions (p < 0.01). The proposed MRI technique should have important applications in various neurological diseases, such as in stroke and brain tumours

A framework for motion correction of background suppressed arterial spin labeling perfusion images acquired with simultaneous multi-slice EPI

Purpose: When employing simultaneous multi-slice (SMS-) EPI for background suppressed (BGS-) arterial spin labeling (ASL), correction of through-plane motion could introduce artefacts, since the slices with most effective BGS are adjacent to slices with the least BGS. In this study, a new framework is presented to correct for such artefacts. Methods: The proposed framework consists of three steps: (i) homogenization of the static tissue signal over the different slices to eliminate most inter-slice differences due to different levels of BGS, (ii) motion correction is applied, (iii) extraction of perfusion-weighted signal using a general linear model. The proposed framework was evaluated by simulations and a functional ASL-study with intentional head-motion. Results: Simulation studies demonstrated that the strong signal differences between slices with the most and least effective BGS caused sub-optimal estimation of motion parameters when through-plane motion was present. Although use of the M0-image as the reference for registration allowed 82% improvement of motion estimation for through-plane motion, it still led to residual subtraction errors caused by different static tissue signal between control and label due to different BGS-levels. By using our proposed framework, those problems were minimized and the accuracy of CBF-estimation was improved. Moreover, the functional ASL-study showed improved detection of visual and motor activation when applying the framework as compared to conventional motion correction, as well as when motion correction was completely omitted. Conclusion: When combining BGS-ASL with SMS-EPI, particular attention is needed to avoid artefacts introduced by motion correction. With the proposed framework these issues are minimized

Time-encoded golden angle radial arterial spin labeling: simultaneous acquisition of angiography and perfusion data

The goal of the current study was to combine a time-encoded pseudo-continuous arterial spin labeling (te-pCASL) scheme with a golden angle radial readout for simultaneous acquisition of angiography and perfusion images from one single dataset both in a very flexible single-slice approach as well as within a multi-slice setting. A te-pCASL labeling preparation and the golden angle radial readout were both used as a temporal resolution tool to retrospectively choose the temporal window for the reconstruction of both angiography and perfusion images from a single-slice dataset. The temporal window could be chosen retrospectively and adjusted to the hemodynamics of the volunteer on the scanner for the single-slice dataset. Angiographic images were reconstructed at a minimum temporal resolution of 69 ms. For the perfusion phase only the densely sampled center of k-space was included in the reconstruction. For a multi-slice acquisition, the golden angle radial readout allowed reconstruction of images with different spatial resolutions to provide angiographic and perfusion information over 10 slices. The te-pCASL preparation was used as the only source for dynamic information. The multi-slice acquisition shows the ability of the golden angle radial readout to display the inflow of the labeled blood into the arteries as well as the perfusion in the tissue with full brain coverage. By combining a te-pCASL preparation with a golden angle radial readout, single-slice high temporal resolution angiography and good quality perfusion images were reconstructed in a flexible manner from a single dataset. Optimizing the golden angle radial readout for reconstructions at multiple spatial resolutions, allows for multi-slice acquisition

Cerebral blood flow and cerebrovascular reactivity are preserved in a mouse model of cerebral microvascular amyloidosis

International audienceImpaired cerebrovascular function is an early biomarker for cerebral amyloid angiopathy (CAA), a neurovascular disease leading to stroke and dementia. The transgenic Swedish Dutch Iowa (Tg-SwDI) mouse model is a model for microvascular CAA, but the extent to which the model reflects similar impairments in cerebrovascular function is not yet fully understood. We used arterial spin labeling (ASL)-MRI and laser Doppler flowmetry (LDF) for extensive functional assessment of the Tg-SwDI brain vasculature using a longitudinal study design. Mice were followed-up until 1 year of age, when extensive amyloid-✂ pathology was visible. Unexpectedly, baseline cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to a hypercapnia challenge in Tg-SwDI mice showed similar estimates as age-matched wild type control mice. The preserved vascular function was found irrespective of the anesthesia protocol applied, i.e., isoflurane or a combination of urethane and-chloralose. Changes in CBF and CVR were however observed as an effect of age and anesthesia. Our findings contradict earlier results obtained in the same mouse model and question to what extent microvascular CAA as seen in Tg-SwDI mice is representative for cerebrovascular dysfunction observed in CAA patients