Jamie M Kawadler

• PhD
• Research Associate at University College London

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. Childre...

Silent cerebral infarction (SCI) is the most commonly reported radiological abnormality in patients with sickle cell anemia (SCA) and is associated with future clinical stroke risk. To date, there have been few histological and quantitative MRI studies of SCI and multiple radiological definitions exist. As a result, the tissue characteristics and c...

In recent years, interest has grown in the potential for magnetic resonance imaging (MRI) measures of venous oxygen saturation (Yv) to improve neurological risk prediction. T2-relaxation-under-spin-tagging (TRUST) is an MRI technique which has revealed changes in Yv in patients with sickle cell anemia (SCA). However, prior studies comparing Yv in p...

In sickle cell disease (SCD), the relative importance of reduced hemoglobin and peripheral oxygen saturation (SpO2) on brain structure remains uncertain. We applied graph-theoretical analysis to diffusion MRI data to investigate the effect of structural brain connectivity on cognitive function, alongside presence/absence, number and volume of silen...

Research in sickle cell anemia (SCA) has used, with limited race-matched control data, binary categorization of patients according to the presence or absence of silent cerebral infarction (SCI). SCI have primarily been identified using low-resolution MRI, with radiological definitions varying in lesion length and the requirement for abnormality on...

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...

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 (CaO 2 ), disease-modifying treatments, silent cerebral infarction...

Background: Sickle cell anemia (SCA) is associated with cognitive challenges that often worsen as children age. Previous work has established relationships between hematological markers of disease severity (i.e., hemoglobin concentration) and various neurological outcomes, including cognitive impairment. However, most studies have related static, o...

Sickle cell disease (SCD) refers to a group of inherited blood disorders with considerable morbidity that causes severe pain, reduces life expectancy, and requires significant self-management. Acute painful episodes are the hallmark of SCD, but persistent daily pain is also highly prevalent in this population. Characterising the impact and experien...

p>Background and Purpose: widespread reductions in white matter integrity are associated with cognitive dysfunction in sickle cell anemia. Silent cerebral infarction (SCI), vasculopathy (VSC), and low hemoglobin concentration (Hb) are implicated; we aimed to determine independent contributions to microstructural white matter injury and whether whit...

We compared the results of Quantitative Susceptibility Mapping (QSM) in each of the Proton Density (PD-), Magnetization Transfer (MT-) and T1-weighted Multi-Echo Gradient-Echo (ME-GRE) sequences in Multi-Parametric Mapping (MPM) with QSM from a conventional ME-GRE sequence. In deep grey matter (GM) regions, we found significant susceptibility (χ) c...

In 15 homozygous sickle-cell disease patients (SCD; hemoglobin-SS) and 12 healthy controls (HC; 10 Hb-AA, 2 Hb-AS), we compared a quantitative susceptibility mapping (QSM)-based estimate of venous oxygen saturation (Yv) with T2-relaxation-under-spin-tagging (TRUST)-based estimates using bovine-hemoglobin (TRUST-HbBV), hemoglobin-S (TRUST-HbS), or h...

Background: Cerebral infarcts and vasculopathy in neurologically asymptomatic children with sickle cell anemia (SCA) have received little attention in African settings. This study aimed to establish the prevalence of silent cerebral infarcts (SCI) and vasculopathy and determine associations with exposure to chronic hemolysis, anemia, and hypoxia....

It is well-established that patients with sickle cell disease (SCD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review m...

Pain burden assessments are essential to evaluate the effectiveness of interventions in sickle cell anaemia (SCA) treatment trials. Number of days in pain or number of hospital admissions are commonly utilised but these measures overlook additional important clinical information captured in complex pain diaries that are challenging to quantify and...

Sickle Cell Anaemia (SCA) is a genetic condition characterized by haemolytic anaemia, cerebral vasculopathy and cognitive impairment. The effect of SCA on brain iron concentrations has not been extensively studied. Brain iron is important in cognitive function and iron overload may accelerate neurodegeneration. Here, susceptibility mapping (QSM) wa...

Ischemic stroke is a common and severe occurrence in Sickle Cell Anaemia (SCA) but no accurate screening measures currently exist for adults. Changes in venous oxygen saturation (Y_{v}) have been suggested as a potential biomarker but measuring Y_{v} in vivo is challenging. This work explores the potential of MRI susceptibility mapping to measure Y...

Objective: The purpose of this retrospective cross-sectional study was to investigate whether changes in white matter integrity are related to slower processing speed in sickle cell anemia. Methods: Thirty-seven patients with silent cerebral infarction, 46 patients with normal MRI, and 32 sibling controls (age range 8-37 years) underwent cogniti...

Children with sickle cell disease (SCD) are at risk of hypoxic exposure due to complications such as chest crisis and sleep apnoea and are more likely to develop cognitive difficulties over time. Although intermittent hypoxia impairs verbal learning and spatial memory in animal models, there are few data on any association of potential reversible m...

Background: Children with sickle cell disease (SCD) are at risk ofhypoxic exposure due to complications such as chest crisis and sleepapnoea and are more likely to develop cognitive difficulties overtime. Although intermittent hypoxia impairs verbal learning and spa-tial memory in animal models, there are few data on any associationof potential reve...

Background: Children with sickle cell disease (SCD) are at risk of hypoxic exposure due to complications such as chest crisis and sleep apnoea and are more likely to develop cognitive difficulties over time. Although intermittent hypoxia impairs verbal learning and spatial memory in animal models, there are few data on any association of potential...

Sickle cell anaemia (SCA) is associated with chronic anaemia and oxygen desaturation, which elevate cerebral blood flow (CBF) and increase the risk of neurocognitive complications. Arterial spin labelling (ASL) provides a methodology for measuring CBF non‐invasively; however, ASL techniques using only a single inflow time are not sufficient to full...

Abstract Background In addition to pain, sickle cell anaemia (HbSS) complications include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation compounded by obstructive sleep apnoea (OSA). In the general population OSA is treated with continuous positive airways pressure (CPAP)....

Regional iron concentrations in the brains of children with Sickle Cell Anaemia Regional iron concentrations in the brains of children with Sickle Cell Anaemia (SCA) were examined using susceptibility mapping (SM), in the (SCA) were examined using susceptibility mapping (SM), in the fifirst study to apply rst study to apply SM to an African cohort...

Sleep Disordered Breathing in Sickle Cell Disease: Impact on Executive Function and Processing Speed Index

Aim: Homozygous sickle cell anaemia (SCA; HbSS) is associated with neurological compromise and attention difficulties. Previous work has shown tentative links between executive dysfunction and daytime oxygen desaturation in SCA. Previous work has not however examined the effects of nocturnal oxygen saturation on attention, nor has it considered whe...

Aim Several complications of sickle cell anaemia, including pain, cardiac dysfunction, stroke, silent cerebral infarction (SCI) and cognitive dysfunction appear to be related to low daytime and night-time oxygen saturation (SpO2). SCA complications can be made worse if patients have extra dips in night time oxygen levels when the upper airway close...

Aims There is substantial evidence that attention is significantly affected in children with a history of stroke. However, which domains of attention are affected and how lesion characteristics (volume, location and age at stroke) affect attention difficulties is unclear. Methods We conducted a systematic review of the current literature to addres...

The pathophysiology of cognitive impairment in sickle cell anemia (SCA) is poorly understood, but may relate to white matter abnormalities. We assessed 84 patients and 18 sibling controls using the Wechsler intelligence scales. In patients, we conducted tract-based spatial statistics analyses of diffusion tensor and neurite orientation dispersion a...

Background: Sickle cell anaemia (SCA) is associated with frequent episodes of vaso-occlusive pain crises, but many patients also experience chronic daily pain, which may be due to avascular necrosis of joints, bone infarction, osteomyelitis or due to intractable chronic pain without obvious pathology2 or neuropathic pain3. Not all patients experien...

Objective: Sickle cell disease (SCD) is associated with neurologic morbidity and cognitive impairments. Lower IQ is well established, but slower processing has received less attention. This review therefore sought to elucidate differences in processing speed index (PSI) between children with SCD, stratified by presence of stroke, and controls. Met...

Cerebrovascular disease (cerebral infarction, intracranial haemorrhage, vasculopathy) are common manifestations of SCD associated with significant morbidity and mortality. These neurological complications and potential corresponding neuropsychological compromise may have devastating consequences for a child with SCD. This chapter aims to review the...

Individual differences in cognitive ability and social behaviour are influenced by the variability in the structure and function of the limbic system. A strong heritability of the limbic cortex has been previously reported, but little is known about how genetic factors influence specific limbic networks. We used diffusion tensor imaging tractograph...

Aim: Sickle cell disease (SCD) is the commonest cause of childhood stroke worldwide. Magnetic resonance imaging (MRI) is routinely used to detect additional silent cerebral infarction (SCI), as IQ is lower in SCI as well as stroke. This review assesses the effect of infarction on IQ, and specifically whether, compared to healthy controls, IQ diffe...

Iron is paramagnetic, accumulates with age, is higher in the deep gray matter in neurodegeneration and if increased in tissues, shortens MRI T1 and T2. There are few data in children with sickle cell disease (SCD). Our aims were to measure T2-weighted signal intensity ratio (T2SIR), a ratio comparing regional T2 with CSF T2, as a proxy for brain ir...

Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. A whole-brain t...

Sickle cell anaemia (SCA) is a genetic disorder affecting haemoglobin. Previous studies suggest that the iron content in some deep-brain regions is higher in transfused SCA patients (TSCA) than in healthy controls (HC). We hypothesised that iron content in those regions is lower in non-transfused patients (NSCA) than in controls as NSCA have low ha...

Sickle Cell Disease (SCD) is a collection of genetic haemoglobinopathies, the most common and severe being homozygous sickle cell anaemia. In the UK, it has been estimated that 1 in 2000 children are born with SCD. The disease is characterised by chronic anaemia, recurrent pain crises and vascular occlusion. Neurologically, there is a high incidenc...

Background: Severe congenital visual impairment (VI) possibly impacts on motor development because of lack of visuo-motor activity from birth, though very limited systematic research has investigated associated neural pathways. The present study investigated if differences are found in diffusion parameters within the cortico-spinal tract between ch...

The human brain changes structurally and functionally during adolescence, with associated alterations in cerebral perfusion. We performed dynamic arterial spin labeling (ASL) magnetic resonance imaging in healthy subjects between 8 and 32 years of age, to investigate changes in cerebral hemodynamics during normal development. In addition, an invers...

Sickle cell anaemia (SCA) is associated with silent cerebral infarction (SCI), affecting white and cortical grey matter, but there are few data on subcortical volumes. We analysed retrospective magnetic resonance imaging (MRI) data in 26 SCA patients and 20 controls, comparing mean subcortical volumes between three groups: controls, SCA with SCI (n...

The OPCRIT program is a symptom checklist with accompanying algorithms producing operationally defined diagnoses. We undertook a review of studies which had used OPCRIT and had reported statistics concerning its reliability and validity, producing summary measures from 44 studies. The first main measure of interest was inter-rater reliability where...

Sickle cell anaemia (SCA) is associated with silent cerebral infarction (SCI), affecting white and cortical grey matter, but there are few data on subcortical volumes. We analysed retrospective magnetic resonance imaging (MRI) data in 26 SCA patients and 20 controls, comparing mean subcortical volumes between three groups: controls , SCA with SCI (...

The human brain changes structurally and functionally during adolescence, with associated alterations in cerebral perfusion. We performed dynamic arterial spin labeling (ASL) magnetic resonance imaging in healthy subjects between 8 and 32 years of age, to investigate changes in cerebral hemodynamics during normal development. In addition, an invers...