Summary
Brain injury is a common complication of sickle cell anaemia (SCA). White matter (WM) and cortical and subcortical grey matter (GM), structures may have reduced volume in patients with SCA. ...This study focuses on whether silent cerebral infarction (SCI), vasculopathy or anaemia affects WM and regional GM volumes in children living in Africa. Children with SCA (n = 144; aged 5–20 years; 74 male) and sibling controls (n = 53; aged 5–17 years; 29 male) underwent magnetic resonance imaging. Effects of SCI (n = 37), vasculopathy (n = 15), and haemoglobin were assessed. Compared with controls, after adjusting for age, sex and intracranial volume, patients with SCA had smaller volumes for WM and cortical, subcortical and total GM, as well as bilateral cerebellar cortex, globus pallidus, amygdala and right thalamus. Left globus pallidus volume was further reduced in patients with vasculopathy. Putamen and hippocampus volumes were larger in patients with SCA without SCI or vasculopathy than in controls. Significant positive effects of haemoglobin on regional GM volumes were confined to the controls. Patients with SCA generally have reduced GM volumes compared with controls, although some subcortical regions may be spared. SCI and vasculopathy may affect the trajectory of change in subcortical GM and WM volume. Brain volume in non‐SCA children may be vulnerable to contemporaneous anaemia.
Previous studies have pointed to a role for regional cerebral hemodynamic stress in neurological complications in patients with sickle cell anemia (SCA), with watershed regions identified as ...particularly at risk of ischemic tissue injury. Using single- and multi-inflow time (TI) arterial spin labeling sequences (ASL) in 94 patients with SCA and 42 controls, the present study sought to investigate cerebral blood flow (CBF) and bolus arrival times (BAT) across gray matter, white matter with early arrival times, and in individual watershed areas (iWSAs). In iWSAs, associations between hemodynamic parameters, lesion burden, white matter integrity, and general cognitive performance were also explored. In patients, increases in CBF and reductions in BAT were observed in association with reduced arterial oxygen content across gray matter and white matter with early arrival times using both sequences (all
< 0.001, d = -1.55--2.21). Across iWSAs, there was a discrepancy between sequences, with estimates based on the single-TI sequence indicating higher CBF in association with reduced arterial oxygen content in SCA patients, and estimates based on the multi-TI sequence indicating no significant between-group differences or associations with arterial oxygen content. Lesion burden was similar between white matter with early arrival times and iWSAs in both patients and controls, and using both sequences, only trend-level associations between iWSA CBF and iWSA lesion burden were observed in patients. Further, using the multi-TI sequence in patients, increased iWSA CBF was associated with reduced iWSA microstructural tissue integrity and slower processing speed. Taken together, the results highlight the need for researchers to consider BAT when estimating CBF using single-TI sequences. Moreover, the findings demonstrate the feasibility of multi-TI ASL for objective delineation of iWSAs and for detection of regional hemodynamic stress that is associated with reduced microstructural tissue integrity and slower processing speed. This technique may hold promise for future studies and treatment trials.
Dystrophic muscles show a high variability of fibre sizes and altered sarcolemmal integrity, which are typically assessed by histology. Time‐dependent diffusion MRI is sensitive to tissue ...microstructure and its investigation through age‐related changes in dystrophic and healthy muscles may help the understanding of the onset and progression of Duchenne muscular dystrophy (DMD).
We investigated the capability of time‐dependent diffusion MRI to quantify age and disease‐related changes in hind‐limb muscle microstructure between dystrophic (mdx) and wild‐type (WT) mice of three age groups (7.5, 22 and 44 weeks).
Diffusion time‐dependent apparent diffusion coefficients (ADCs) of the gastrocnemius and tibialis anterior muscles were determined versus age and diffusion‐gradient orientation at six diffusion times (Δ; range: 25–350 ms). Mean muscle ADCs were compared between groups and ages, and correlated with T2, using Student's t test, one‐way analysis of variance and Pearson correlation, respectively. Muscle fibre sizes and sarcolemmal integrity were evaluated by histology and compared with diffusion measurements.
Hind‐limb muscle ADC showed characteristic restricted diffusion behaviour in both mdx and WT animals with decreasing ADC values at longer Δ. Significant differences in ADC were observed at long Δ values (≥ 250 ms; p < 0.05, comparison between groups; p < 0.01, comparison between ages) with ADC increased by 5–15% in dystrophic muscles, indicative of reduced diffusion restriction. No significant correlation was found between T2 and ADC. Additionally, muscle fibre size distributions showed higher variability and lower mean fibre size in mdx than WT animals (p < 0.001). The extensive Evans Blue Dye uptake shown in dystrophic muscles revealed substantial sarcolemmal damage, suggesting diffusion measurements as more consistent with altered permeability rather than changes in muscle fibre sizes.
This study shows the potential of diffusion MRI to non‐invasively discriminate between dystrophic and healthy muscles with enhanced sensitivity when using long Δ.
We investigated the sensitivity of time‐dependent diffusion MRI to quantify age and disease‐related changes in hind‐limb muscle microstructure between dystrophic and wild‐type mice. Muscle water diffusivity was higher in mdx than wild‐type mice particularly at long diffusion times (Δ ≥ 250 ms). On the other hand, histological findings showed that mean muscle fibre size was reduced in dystrophic muscles while sarcolemma permeability was greatly enhanced. This suggests that sarcolemmal permeability was the largest factor in determining muscle ADC.
Patients with advanced heart failure have a dismal prognosis and poor quality of life. Heart transplantation provides an effective treatment for a subset of these patients. This article provides ...cardiologists with up-to-date information about referral for transplantation, the role of left ventricular assist devices prior to transplant, patient selection, waiting-list management and donor heart availability. Timing is of central importance; patients should be referred before complications (eg, cardiorenal syndrome or secondary pulmonary hypertension) have developed that will increase the risk of, or potentially contraindicate, transplantation. Issues related to heart failure aetiology, comorbidity and adherence to medical treatment are reviewed. Finally, the positive role that cardiologists can play in promoting and facilitating organ donation is discussed.
A greater extent of resection of the temporal portion of the piriform cortex (PC) has been shown to be associated with higher likelihood of seizure freedom in adults undergoing anterior temporal lobe ...resection (ATLR) for drug-resistant temporal lobe epilepsy (TLE). There have been no such studies in children, therefore this study aimed to investigate this association in a pediatric cohort.
A retrospective, neuroimaging cohort study of children with TLE who underwent ATLR between 2012 and 2021 was undertaken. The PC, hippocampal and amygdala volumes were measured on the preoperative and postoperative T1-weighted MRI. Using these volumes, the extent of resection per region was compared between the seizure-free and not seizure-free groups.
In 50 children (median age 9.5 years) there was no significant difference between the extent of resection of the temporal PC in the seizure-free (median = 50%, n = 33/50) versus not seizure-free (median = 40%, n = 17/50) groups (p = 0.26). In a sub-group of 19 with ipsilateral hippocampal atrophy (quantitatively defined by ipsilateral-to-contralateral asymmetry), the median extent of temporal PC resection was greater in children who were seizure-free (53%) versus those not seizure-free (19%) (p = 0.009).
This is the first study demonstrating that, in children with TLE and hippocampal atrophy, more extensive temporal PC resection is associated with a greater chance of seizure freedom-compatible with an adult series in which 85% of patients had hippocampal sclerosis. In a combined group of children with and without hippocampal atrophy, the extent of PC resection was not associated with seizure outcome, suggesting different epileptogenic networks within this cohort.
Prematurity presents a risk for higher order cognitive functions. Some of these deficits manifest later in development, when these functions are expected to mature. However, the causes and ...consequences of prematurity are still unclear. We conducted a longitudinal study to first identify clinical predictors of ultrasound brain abnormalities in 196 children born very preterm (VP; gestational age ≤32 weeks) and with very low birth weight (VLBW; birth weight ≤1500 g). At ages 8–16, the subset of VP-VLBW children without neurological findings (124) were invited for a neuropsychological assessment and an MRI scan (41 accepted). Of these, 29 met a rigorous criterion for MRI quality and an age, and gender-matched control group (
n
= 14) was included in this study. The key findings in the VP-VLBW neonates were: (a) 37% of the VP-VLBW neonates had ultrasound brain abnormalities; (b) gestational age and birth weight collectively with hospital course (i.e., days in hospital, neonatal intensive care, mechanical ventilation and with oxygen therapy, surgeries, and retinopathy of prematurity) predicted ultrasound brain abnormalities. At ages 8–16, VP-VLBW children showed: a) lower intelligent quotient (IQ) and executive function; b) decreased gray and white matter (WM) integrity; (c) IQ correlated negatively with cortical thickness in higher order processing cortical areas. In conclusion, our data indicate that facets of executive function and IQ are the most affected in VP-VLBW children likely due to altered higher order cortical areas and underlying WM.
The optic radiation (OR) is a component of the visual system known to be myelin mature very early in life. Diffusion tensor imaging (DTI) and its unique ability to reconstruct the OR in vivo were ...used to study structural maturation through analysis of DTI metrics in a cohort of 90 children aged 5–18 years. As the OR is at risk of damage during epilepsy surgery, we measured its position relative to characteristic anatomical landmarks. Anatomical distances, DTI metrics and volume of the OR were investigated for age, gender and hemisphere effects. We observed changes in DTI metrics with age comparable to known trajectories in other white matter tracts. Left lateralization of DTI metrics was observed that showed a gender effect in lateralization. Sexual dimorphism of DTI metrics in the right hemisphere was also found. With respect to OR dimensions, volume was shown to be right lateralised and sexual dimorphism demonstrated for the extent of the left OR. The anatomical results presented for the OR have potentially important applications for neurosurgical planning.
Prior studies have described high venous signal qualitatively using arterial spin labelling (ASL) in patients with sickle cell anemia (SCA), consistent with arteriovenous shunting. We aimed to ...quantify the effect and explored cross-sectional associations with arterial oxygen content (CaO2), disease-modifying treatments, silent cerebral infarction (SCI), and cognitive performance. 94 patients with SCA and 42 controls underwent cognitive assessment and MRI with single- and multi- inflow time (TI) ASL sequences. Cerebral blood flow (CBF) and bolus arrival time (BAT) were examined across gray and white matter and high-signal regions of the sagittal sinus. Across gray and white matter, increases in CBF and reductions in BAT were observed in association with reduced CaO2 in patients, irrespective of sequence. Across high-signal sagittal sinus regions, CBF was also increased in association with reduced CaO2 using both sequences. However, BAT was increased rather than reduced in patients across these regions, with no association with CaO2. Using the multiTI sequence in patients, increases in CBF across white matter and high-signal sagittal sinus regions were associated with poorer cognitive performance. These novel findings highlight the utility of multiTI ASL in illuminating, and identifying objectively quantifiable and functionally significant markers of, regional hemodynamic stress in patients with SCA.
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