Biology subjects

Wheeler-Kingshott, C. A. M. G.

Publications and source records attributed to Wheeler-Kingshott, C. A. M. G..

3 recordsLinked to original sources

bioRxiv2023

Quantification of water exchange across the blood-brain barrier using non-contrast MR fingerprinting

PurposeA method is proposed to quantify cerebral blood volume (vb) and intravascular water residence time ({tau}b) using magnetic resonance fingerprinting (MRF), applied using a spoiled gradient echo sequence, without the need for contrast agent. MethodsAn in silico study optimised an acquisition protocol to maximise the sensitivity of the measurement to vb and{tau} b changes. Its accuracy in the presence of variations in T1,t, T1,b, and B1 was evaluated. The optimised protocol (scan time of 19 minutes) was then tested in a exploratory healthy volunteer study (10 volunteers, mean age 24 {+/-} 3, 6 male) at 3 T with a repeat scan taken after repositioning to allow estimation of repeatability. ResultsSimulations show that assuming literature values for T1,b and T1,t, no variation in B1, while fitting only vb and{tau} b, leads to large errors in quantification of vb and{tau} b, regardless of noise levels. However, simulations also show that matching [Formula] and{tau} b, simultaneously is feasible at clinically achievable noise levels. Across the healthy volunteers, all parameter quantifications fell within the expected literature range. In addition, the maps show good agreement between hemispheres suggesting physiologically relevant information is being extracted. Expected differences between white and grey matter T1,t (p<0.0001) and vb (p<0.0001) are observed, T1,b and{tau} b show no significant differences, p=0.4 and p=0.6 repectively. Good repeatability was seen between repeat scans: mean ICC of T1,t : 0.91, T1,b : 0.58, vb : 0.90, and v{tau}b : 0.96. ConclusionWe demonstrate that regional simultaneous quantification of vb,{tau} b, T1,b,T1,t, and B1 using MRF is feasible in vivo.

neuroscience↗

bioRxiv2023

Structural and connectivity parameters reveal compensation patterns in young patients with non-progressive and slow-progressive cerebellar ataxia

IntroductionWithin Pediatric Cerebellar Ataxias (PCAs), patients with non-progressive ataxia (NonP) surprisingly show postural motor behavior comparable to that of healthy controls, differently to slow-progressive ataxia patients (SlowP). This difference may depend on the building of the compensatory strategies of the intact areas in NonP brain network. MethodsEleven PCAs patients were recruited: five with NonP and six with SlowP. We assessed volumetric and axonal bundles alterations with a multimodal approach to investigate the connections between basal ganglia and cerebellum as putative compensatory tracts. ResultsCerebellar lobules were smaller in SlowP patients. NonP patients showed a lower number of streamlines in the cerebello-thalamo-cortical tracts but a generalized higher integrity of white matter tracts connecting the cortex and the basal ganglia with the cerebellum. DiscussionThis work reveals that the axonal bundles connecting the cerebellum with basal ganglia and cortex demonstrate a higher integrity in NonP patients. This evidence highlights the importance of the cerebellum-basal ganglia connectivity to explain the different postural motor behavior of NonP and SlowP patients and support the compensatory role of basal ganglia in patients with stable cerebellar malformation.

neuroscience↗

bioRxiv2017

Deep grey matter volume loss drives disability worsening in multiple sclerosis

ObjectiveGrey matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS.\n\nMethodsWe analysed 3,604 brain high-resolution T1-weighted MRI scans from 1,417 participants: 1,214 MS patients (253 clinically-isolated syndrome[CIS], 708 relapsingremitting[RRMS], 128 secondary-progressive[SPMS], 125 primary-progressive[PPMS]), over an average follow-up of 2.41 years (standard deviation[SD]=1.97), and 203 healthy controls (HCs) [average follow-up=1.83 year, SD=1.77], attending 7 European centres. Disability was assessed with the Expanded-Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem and cerebral white matter. Hierarchical mixed-models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-EDSS progression.\n\nResultsSPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio=0.73, 95% CIs 0.65, 0.82; p<0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%) and HCs (-0.94%)[p<0.01]. The rate of temporal GM atrophy in SPMS (-1.21%) was significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%). Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS (-0.63%) and HCs (-0.23%) (all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta=0.04, p<0.001).\n\nInterpretationThis large multi-centre and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions.

neuroscience↗