White Matter Volume Reduction Research Articles

Discriminative Analysis of Depression Patients Studied with Structural MR Images Using Support Vector Machine and Recursive Feature Elimination

Currently, the diagnosis of depression is largely based on clinical judgments due to the absence of objective biomarkers. There are increasing evidences that depression (DP) is associated with structural abnormalities. However, the previous analyses have a poor predictive power for individuals. To discriminate DP patients from normal controls (NCs) studied with structural magnetic resonance images using the method of support vector machine (SVM) combined with recursive feature elimination (RFE). In this study, 40 DP patients and 40 age- and sex-matched NCs were recruited from Guangzhou Brain Hospital and the local community, respectively. We calculated gray matter volume (GMV) and white matter volume (WMV) of 210 cortical and 36 subcortical regions, defined by the Human Brainnetome Atlas. The group differences between DP patients and NCs were compared. The method of SVM combined with RFE was applied into the discriminative analysis of DP patients from NCs, in which discriminative features were drawn from GMV and WMV. We found that the DP patients showed significant GMV reductions in eight brain regions and showed significant WMV reductions in ten brain regions. The classifier using GMV as input features achieved the best performance (an accuracy of 86.25%, a sensitivity of 85%, and a specificity of 87.5%) in the discriminative analyses between DP patients and NCs. These findings provided evidences that specific structural brain regions associated with DP patients might qualify as a potential biomarker for disease diagnosis, and the machine-learning method of SVM with RFE may reveal neurobiological mechanisms in distinguishing DP patients from NCs.

Reduced Neurosteroid Exposure Following Preterm Birth and Its' Contribution to Neurological Impairment: A Novel Avenue for Preventative Therapies.

Children born preterm are at an increased risk of developing cognitive problems and neuro-behavioral disorders such as attention deficit hyperactivity disorder (ADHD) and anxiety. Whilst neonates born at all gestational ages, even at term, can experience poor cognitive outcomes due to birth-complications such as birth asphyxia, it is becoming widely known that children born preterm in particular are at significant risk for learning difficulties with an increased utilization of special education resources, when compared to their healthy term-born peers. Additionally, those born preterm have evidence of altered cerebral myelination with reductions in white matter volumes of the frontal cortex, hippocampus and cerebellum evident on magnetic resonance imaging (MRI). This disruption to myelination may underlie some of the pathophysiology of preterm-associated brain injury. Compared to a fetus of the same post-conceptional age, the preterm newborn loses access to in utero factors that support and promote healthy brain development. Furthermore, the preterm ex utero environment is hostile to the developing brain with a myriad of environmental, biochemical and excitotoxic stressors. Allopregnanolone is a key neuroprotective fetal neurosteroid which has promyelinating effects in the developing brain. Preterm birth leads to an abrupt loss of the protective effects of allopregnanolone, with a dramatic drop in allopregnanolone concentrations in the preterm neonatal brain compared to the fetal brain. This occurs in conjunction with reduced myelination of the hippocampus, subcortical white matter and cerebellum; thus, damage to neurons, astrocytes and especially oligodendrocytes of the developing nervous system can occur in the vulnerable developmental window prior to term as a consequence reduced allopregnanolone. In an effort to prevent preterm-associated brain injury a number of therapies have been considered, but to date, other than antenatal magnesium sulfate and corticosteroid therapy, none have become part of standard clinical care for vulnerable infants. Therefore, there remains an urgent need for improved therapeutic options to prevent brain injury in preterm neonates. The actions of the placentally derived neurosteroid allopregnanolone on GABAA receptor signaling has a major role in late gestation neurodevelopment. The early loss of this intrauterine neurotrophic support following preterm birth may be pivotal to development of neurodevelopmental morbidity. Thus, restoring the in utero neurosteroid environment for preterm neonates may represent a new and clinically feasible treatment option for promoting better trajectories of myelination and brain development, and therefore reducing neurodevelopmental disorders in children born preterm.

Progressive brain structural changes after the first year of treatment in first-episode treatment-naive patients with deficit or nondeficit schizophrenia

Progressive brain volume atrophy has been reported in patients with schizophrenia. However, whether this progress differs between patients with primary negative symptoms (deficit schizophrenia; DS) and those without such symptoms (nondeficit schizophrenia; NDS) is unknown. Here, we examined grey matter volume (GMV) and white matter volume (WMV) changes over 12 months in 34 first-episode treatment-naive patients with schizophrenia (14 DS and 20 NDS) and 32 healthy controls (HCs) using structural magnetic resonance imaging and voxel-based morphometry. At baseline, compared to HCs, patients with DS but not NDS had less WMV in bilateral posterior limb of the internal capsule (PLIC) and cerebellar tonsil (P < 0.05, FDR corrected) and smaller GMV in the cerebellar culmen (P < 0.05, FWE corrected). At follow-up, NDS group showed WMV reduction in bilateral PLIC (P < 0.05, FDR corrected), while DS group showed no progressive WMV changes. While both patient groups exhibited GMV reduction in the hippocampus and insular cortex, patients with NDS showed additional GMV loss in the frontal and cingulate cortex and a selective increase in GMV in the left thalamus (P < 0.05 FWE corrected). Our study revealed double dissociations in developmental brain volume changes in the first year after clinical contact for psychosis in DS versus NDS patients.

Childhood multiple sclerosis is associated with reduced brain volumes at first clinical presentation and brain growth failure

Background: Paediatric multiple sclerosis (pedMS) patients at a single site were shown to have reduced brain volumes and failure of age-expected brain growth compared to healthy controls. However, the precise time of onset of brain volume loss remains unclear. Objective: To longitudinally study brain volumes in a multi-centre European cohort at first presentation and after 2 years. Methods: Brain volumes of high-resolution magnetic resonance imaging (MRI) data from 37 pedMS patients at first presentation prior to steroid therapy and at 2-year follow-up (n = 21) were compared to matched longitudinal MRI data from the NIH Paediatric MRI Data Repository. Results: Patients showed significantly reduced whole brain, grey and white matter and increased ventricular volumes at initial presentation and at follow-up compared to controls. Over 2 years, patients exhibited significant reduction of whole brain and white matter volumes, accompanied by increased ventricular volume. Brain volume loss at follow-up correlated with a higher number of infratentorial lesions, relapses and an increased Expanded Disability Status Scale (EDSS) score. Conclusions: In pedMS patients, brain volume loss is present already at first clinical presentation and accelerated over 2 years. Increased disease activity is associated with more severe brain volume loss. MRI brain volume change might serve as an outcome parameter in future prospective pedMS studies.

Emergent Prophylactic, Reparative and Restorative Brain Interventions for Infants Born Preterm With Cerebral Palsy.

Worldwide, an estimated 15 million babies are born preterm (<37 weeks' gestation) every year. Despite significant improvements in survival rates, preterm infants often face a lifetime of neurodevelopmental disability including cognitive, behavioral, and motor impairments. Indeed, prematurity remains the largest risk factor for the development of cerebral palsy. The developing brain of the preterm infant is particularly fragile; preterm babies exhibit varying severities of cerebral palsy arising from reductions in both cerebral white and gray matter volumes, as well as altered brain microstructure and connectivity. Current intensive care therapies aim to optimize cardiovascular and respiratory function to protect the brain from injury by preserving oxygenation and blood flow. If a brain injury does occur, definitive diagnosis of cerebral palsy in the first few hours and weeks of life is difficult, especially when the lesions are subtle and not apparent on cranial ultrasound. However, early diagnosis of mildly affected infants is critical, because these are the patients most likely to respond to emergent treatments inducing neuroplasticity via high-intensity motor training programs and regenerative therapies involving stem cells. A current controversy is whether to test universal treatment in all infants at risk of brain injury, accepting that some patients never required treatment, because the perceived potential benefits outweigh the risk of harm. Versus, waiting for a diagnosis before commencing targeted treatment for infants with a brain injury, and potentially missing the therapeutic window. In this review, we discuss the emerging prophylactic, reparative, and restorative brain interventions for infants born preterm, who are at high risk of developing cerebral palsy. We examine the current evidence, considering the timing of the intervention with relation to the proposed mechanism/s of action. Finally, we consider the development of novel markers of preterm brain injury, which will undoubtedly lead to improved diagnostic and prognostic capability, and more accurate instruments to assess the efficacy of emerging interventions for this most vulnerable group of infants.

Depression, auditory-verbal hallucinations, and delusions in patients with schizophrenia: Different patterns of association with prefrontal gray and white matter volume

Structural brain abnormalities, including decreased gray matter (GM) and white matter (WM) volume, have been observed in patients with schizophrenia. These decrements were found to be associated with positive and negative symptoms, but affective symptoms (depression and anxiety) were poorly explored. We hypothesized that abnormalities in GM and WM volume might also be related to affective symptoms. GM and WM volumes were calculated from high-resolution T1 structural images acquired from 24 patients with schizophrenia and 26 healthy controls, and the associations of positive, negative, and affective symptoms with the brain volumes that showed significant reduction in patients were investigated. Patients demonstrated GM volume reductions in the bilateral prefrontal cortex, and WM volume reductions in the right frontal and left corpus callosum. Prefrontal cortex volume was significantly and inversely associated with both auditory-verbal hallucinations and depression severity. WM volume alterations, in contrast, were related to alogia, anhedonia, and delusions. The combined impact of auditory-verbal hallucinations and depression on similar sub-regions of the prefrontal cortex suggests that depression is involved in hearing voices. Further, this adverse impact of depression on prefrontal GM volume may underlie the impairment demonstrated by these patients in cognitive tasks that rely on executive processes.

White matter volume is decreased in bipolar disorder at early and late stages.

Bipolar disorder (BD) is a debilitating mood condition that affects approximately 1.3% of people worldwide, although some studies report up to 3.9% lifetime prevalence and 4-6% in adults when broad diagnostic criteria are applied. To compare differences in total white matter (WM), corpus callosum (CC) and total gray matter (GM) volumes in patients with type I BD at early and late stages compared with controls. Fifty-five subjects were enrolled in this study protocol. The double case-control design included 14 patients with BD at early stage; 15 patients at late stage; and their respective matched controls (14 and 12 subjects). CC and total WM volumes were significantly smaller in patients with BD at early and late stages vs. controls. There was no difference for total GM volume in the early stage group, but in patients at late stage total GM volume was significantly smaller than in controls. The total GM volume reduction in patients at late stage is in agreement with the neuroprogression theory of BD. The reduction of WM volumes in total WM and in the CC at early and late stages supports the possibility that an early demyelination process could occur underlying the clinical manifestation of BD. Our findings may direct to the investigation of WM abnormalities in populations at high risk to develop BD, perhaps as early biomarkers before the overt syndrome.

Antipsychotics and Their Impact on Cerebral White Matter: Part of the Problem or Part of the Solution?

Antipsychotics and Their Impact on Cerebral White Matter: Part of the Problem or Part of the Solution?

Evolutionary divergence of neuroanatomical organization and related genes in chimpanzees and bonobos

Given their close genetic relatedness to humans, bonobos (Pan paniscus) and chimpanzees (Pan troglodytes) offer an essential comparative framework for studying the evolution of uniquely human traits. These two species differ markedly in their socio-behavioral repertoires, which is reflected in neuroanatomical differences that have been reported in the literature. However, phylogenetic comparative methods have not yet been used to map the evolution of neuroanatomical traits in bonobos and chimpanzees, limiting our ability to understand which neural systems are derived in each species in relation to the last common ancestor of Pan (Pan-LCA). Here, we examine evolutionary changes in neuroanatomical traits of bonobos and chimpanzees relative to ancestral character reconstructions of the Pan-LCA using comparative datasets from hominoids. We found that bonobo brains are derived in showing reduction of whole brain and white matter volumes, with particularly striking reduction of male brain size compared to the inferred Pan-LCA value. Brain structures related to social cognition and emotional regulation, like the insular cortex and amygdala, display a mosaic pattern of evolution with certain traits changing to a greater extent in each species. Examination of potential genetic mechanisms underlying divergence of neural and social traits did not reveal clear differences in protein evolution patterns between the two species. These findings suggest that the brain anatomy of extant bonobos and chimpanzees show lineage-specific specializations and neither can be considered to more closely retain the ancestral state of Pan. Consequently, this raises questions about the extent that modern chimpanzees or bonobos may serve as referential models for the neuroanatomy of the LCA of humans and apes.

Neuropsychiatric complications and neuroimaging characteristics after deep brain stimulation surgery for Parkinson's disease.

Psychiatric complications after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease patients are common. The aim of this study was to evaluate a possible role of cortical thickness, cortical and subcortical volume for neuropsychiatric complications after STN-DBS implantation surgery. Twenty-two Parkinson's disease patients underwent STN-DBS. Control group consisted of 18 healthy volunteers who were matched by age and gender. All Parkinson's disease patients and control subjects underwent neuropsychological assessment and brain MRI. Control group subjects had normal MRI and neurocognitive testing results. Seven (31.8%) Parkinson's disease patients developed neuropsychiatric complications (psychosis and delirium) after STN-DBS implantation surgery with full recovery in short follow up. Two Parkinson's disease patients were excluded from further analysis, because they did not match image processing and analysis quality control. Volumetric analysis showed significant differences in cortical thickness between STN-DBS patients with and without postoperative neuropsychiatric complications in 13 gyruses on the right hemisphere (superior frontal, caudal middle frontal, pars triangularis and opercularis, temporal lobe, superior and inferior parietal, supramarginal) and in 7 gyruses on the left hemisphere (caudal middle frontal, inferior and middle temporal, pre and postcentral, superior parietal and supramarginal). White matter volume analysis showed also its reduction in the left caudal middle frontal area. Moreover, white matter volume and surface area reduction implicating that this area can be the most important for postoperative neuropsychiatric complication risk. Study results suggest that neuropsychiatric complications are common in Parkinson's disease patients after STN-DBS implantation and can be associated with excitation of frontal-striatum-thalamus and temporal-parietal circuits.

Voxel-based meta-analysis of gray and white matter volume abnormalities in spinocerebellar ataxia type 2.

ObjectiveTo identify the consistent findings from the whole‐brain voxel‐based morphometry (VBM) studies on spinocerebellar ataxia type 2 (SCA2).MethodsThe whole‐brain VBM studies comparing SCA2 patients and healthy controls (HCs) were systematically searched in PubMed, Embase databases from January 2000 to June 2017. The coordinates with significant differences in gray matter (GM) and white matter (WM) between SCA2 patients and HCs were extracted separately from each cluster. A meta‐analysis was performed using anisotropic effect size‐based signed differential mapping (AES‐SDM) software.ResultsA total of five studies with 65 SCA2 patients and 124 HCs were included in the GM meta‐analysis. Four of the five studies with 50 SCA2 patients and 109 HCs were included in the WM meta‐analysis. Significant and consistent GM volume reductions were detected in bilateral cerebellar hemispheres, cerebellar vermis, the right fusiform gyrus, the right parahippocampal gyrus, and the right lingual gyrus. The WM volume reductions were observed in bilateral cerebellar hemispheres, cerebellar vermis, middle cerebellar peduncles, pons, and bilateral cortico‐spinal projections. The findings of the study remained largely unchanged in jackknife sensitivity analysis.ConclusionsThe consistent findings from our meta‐analysis showed that GM volume reductions in SCA2 patients were not limited in cerebellum while significant WM volume reductions widely existed in cerebellum and pyramidal system. The findings provide morphological basis for further studies on SCA2.

Longitudinal changes in brain volumetry and cognitive functions after moderate and severe diffuse axonal injury

ABSTRACTBackground and objective: Diffuse axonal injury (DAI) induces a long-term process of brain atrophy and cognitive deficits. The goal of this study was to determine whether there are correlations between brain volume loss, microhaemorrhage load (MHL) and neuropsychological performance during the first year after DAI.Methods: Twenty-four patients with moderate or severe DAI were evaluated at 2, 6 and 12 months post-injury. MHL was evaluated at 3 months, and brain volumetry was evaluated at 3, 6 and 12 months. The trail making test (TMT) was used to evaluate executive function (EF), and the Hopkins verbal learning test (HVLT) was used to evaluate episodic verbal memory (EVM) at 6 and 12 months.Results: There were significant white matter volume (WMV), subcortical grey matter volume and total brain volume (TBV) reductions during the study period (p < 0.05). MHL was correlated only with WMV reduction. EF and EVM were not correlated with MHL but were, in part, correlated with WMV and TBV reductions.Conclusions: Our findings suggest that MHL may be a predictor of WMV reduction but cannot predict EF or EVM in DAI. Brain atrophy progresses over time, but patients showed better EF and EVM in some of the tests, which could be due to neuroplasticity.

Congenital aqueduct stenosis: Progressive brain findings in utero to birth in the presence of severe hydrocephalus.

To evaluate the effects of progressive hydrocephalus on the developing brain in a cohort of fetuses diagnosed with congenital aqueduct stenosis by comparing prenatal magnetic resonance imaging and postnatal imaging. This IRB approved single center retrospective review of prenatally diagnosed children with congenital aqueduct stenosis interrogated changes in the brain between prenatal and postnatal imaging and analyzed statistics using SAS software package version 9.3. Thirty fetuses imaged at a mean gestational age of 26weeks had aqueduct obstruction confirmed by postnatal imaging. Progressive hydrocephalus required shunting in all but one patient (97%). Those patients with increasing hydrocephalus showed increase in ventricular rupture (60%), loss of septal leaflets (47%), and reduction in white matter and corpus callosum volume (43%). Cerebellar ectopia developed in 27% with 6% meeting the criteria for Chiari I malformation. Hydrocephalus in the fetus results in enlarging ventricular rupture, loss of the septum pellucidum leaflets, volume reduction of brain parenchyma including corpus callosum, and risk for Chiari I anomaly. Given advances in fetal surgery and imaging in the last 3 decades, there may be cause to revisit the idea of in utero cerebral spinal fluid diversion as a means to potentially ameliorate progressive loss of the developing brain.

Gray Matter and White Matter Abnormalities in Temporal Lobe Epilepsy Patients with and without Hippocampal Sclerosis.

The presentation and distribution of gray matter (GM) and white matter (WM) abnormalities in temporal lobe epilepsy (TLE) have been widely studied. Here, we investigated the GM and WM abnormalities in TLE patients with and without hippocampal sclerosis (HS) in five groups of participants: healthy controls (HCs) (n = 28), right TLE patients with HS (n = 26), right TLE patients without HS (n = 30), left TLE patients with HS (n = 25), and left TLE patients without HS (n = 27). We performed a flexible factorial statistical test in a whole-brain voxel-based morphometry analysis to identify significant GM and WM abnormalities and analysis of variance of hippocampal and amygdala regions among the five groups using the FreeSurfer procedure. Furthermore, we conducted multiple regression analysis to assess regional GM and WM changes with disease duration. We observed significant ipsilateral mesiotemporal GM and WM volume reductions in TLE patients with HS compared with HCs. We also observed a slight GM amygdala swelling in right TLE patients without HS. The regression analysis revealed significant negative GM and WM changes with disease duration specifically in left TLE patients with HS. The observed GM and WM abnormalities may contribute to our understanding of the root of epilepsy mechanisms.

Cognitive and psychopathology correlates of brain white/grey matter structure in severely psychotic schizophrenic inpatients

The brain structural correlates of cognitive and psychopathological symptoms within the active phase in severely psychotic schizophrenic inpatients have been rarely investigated. Twenty-eight inpatients with a DSM-5 diagnosis of Schizophrenia (SZ), admitted for acute psychotic decompensation, were assessed through a comprehensive neuropsychological and psychopathological battery. All patients underwent a high-resolution T1-weighted magnetic resonance imaging investigation.Increased psychotic severity was related to reduced grey matter volumes in the medial portion of the right superior frontal cortex, the superior orbitofrontal cortex bilaterally and to white matter volume reduction in the medial portion of the left superior frontal area. Immediate verbal memory performance was related to left insula and inferior parietal cortex volume, while long-term visuo-spatial memory was related to grey matter volume of the right middle temporal cortex, and the right (lobule VII, CRUS1) and left (lobule VI) cerebellum. Moreover, psychotic severity correlated with cognitive inflexibility and negative symptom severity was related to visuo-spatial processing and reasoning disturbances.These findings indicate that a disruption of the cortical-subcortical-cerebellar circuit, and distorted memory function contribute to the development and maintenance of psychotic exacerbation.

Homocysteine and Cerebral Atrophy: The Epidemiology of Dementia in Singapore Study.

Plasma homocysteine levels are increasingly studied as a potential risk factor for dementia. Elevated homocysteine levels have been linked with gray and white matter volume reduction among individuals with mild cognitive impairment and Alzheimer's disease. However, the effects of homocysteine on brain changes in preclinical stages of dementia remain unexplored. To examine the association of elevated homocysteine levels with markers of neurodegeneration, i.e., white and gray matter volume in an elderly population. The study included 768 participants (mean age: 69.6±6.5 years, 51.3% women) from the Epidemiology of Dementia In Singapore study. Participants underwent a brain MRI scan and blood tests. Serum homocysteine was measured using competitive immunoassay. Cortical thickness and subcortical structural volume were quantified using FreeSurfer whereas white matter volume was quantified using a previous validated method. Higher homocysteine levels were significantly associated with decreased global white matter volume [mean difference (β) in volume (ml) per micromole per liter (μmol/l) increase in homocysteine levels: - 0.555, 95% Confidence Interval (CI): - 0.873; - 0.237], decreased parietal cortical thickness [β in thickness (μm) per μmol/l increase in homocysteine levels:- 1.429, 95% CI: - 2.781; - 0.077], and smaller volumes of the thalamus [β: - 0.017, 95% CI: - 0.026; - 0.008], brainstem [β: - 0.037, 95% CI: - 0.058; - 0.016], and accumbens [β: - 0.004, 95% CI: - 0.006; - 0.002]. Higher homocysteine levels were associated with cerebral atrophy. Further studies are required to assess whether lowering plasma homocysteine levels may prevent neurodegenerative changes or delay progression of clinical symptoms before the development of dementia.

Clinical Factors Associated with Brain Volume Reduction in Systemic Lupus Erythematosus Patients without Major Neuropsychiatric Manifestations.

The aim of the study was to find structural brain changes in systemic lupus erythematosus patients without major neuropsychiatric manifestations [non-neuropsychiatric systemic lupus erythematosus (non-NPSLE)] using quantitative magnetic resonance imaging (MRI) and possible associations with clinical characteristics. 89 non-NPSLE patients with normal conventional MRI and 84 healthy controls (HCs) were recruited. The whole brain gray matter volume (GMV) and white matter volume (WMV) were calculated for each individual. We found obvious GMV and WMV reduction in the systemic lupus erythematosus (SLE) group compared with HCs. Female patients showed significant reduction of GMV and WMV compared with male patients. Patients treated with immunosuppressive agents (ISA) showed less WMV reduction than those without. Cognitive impairment was the most common subclinical neuropsychiatric manifestation and had a prevalence of 46.1%. Association between WMV reduction with cognitive impairment was found. Thus, we concluded that structural brain atrophy could happen even before occurrence of obvious neuropsychiatric signs and symptoms and was associated with subclinical symptoms such as cognitive impairment. ISA treatment might have a protective effect on the brain atrophy. Early treatment might prevent the progressive damage to the brain. More studies are needed to fully understand the complicated underlying mechanisms of brain atrophy in SLE.

Candidate molecular pathways of white matter vulnerability in the brain of normal aging rhesus monkeys.

Mammalian aging is associated with decline in cognitive functions. Studies searching for a cause of cognitive aging initially focused on neuronal loss but quantitative investigations of rat, monkey, and human brain using stereology demonstrated that in normal aging, unlike in neurodegenerative disease, neurons are not lost. Instead, electron microscopic and MRI studies in normal aging monkeys revealed age-related damage to myelin sheaths, loss of axons, and reduction in white matter volume which correlates with cognitive impairments. However, little is known about the cause of myelin defects or associated axon loss. The present study investigates the effect of age on signaling pathways between oligodendroglia and neurons using a custom PCR array to assess the expression of 87 genes of interest in cortical gray matter and white matter from the inferior parietal lobe (IPL) of normal rhesus monkeys ranging in age from 4.2 to 30.4years old. From this array data, five target genes of interest were selected for further analysis to confirm gene expression and measure protein expression. The most interesting target gene identified is brain-derived neurotrophic factor (BDNF), which was the only gene that was altered at both mRNA and protein levels. In gray matter, BDNF mRNA was decreased. While the level of the mature form of the protein was unchanged, there was a specific decrease in the precursor form of BDNF. These alterations in the BDNF in gray matter could contribute to the vulnerability and loss of the axons with age.

Voxel-based meta-analysis of gray and white matter volume reductions in spinocerebellar ataxia type 2

Voxel-based meta-analysis of gray and white matter volume reductions in spinocerebellar ataxia type 2

Retrospective assessment of MRI-based volumetric changes of normal tissues in glioma patients following radio(chemo)therapy

In glioma patients, linac-based photon beam irradiation is a widely applied therapy, which achieves highly conformal target volume coverage, but is also known to cause side-effects to adjacent areas of healthy tissue. Apart from subjective measures, such as quality of life assessment and neurocognitive function tests, objective methods to quantify tissue damage are needed to assess this impact. Magnetic resonance imaging (MRI) is a well-established method for brain tumor diagnoses as well as assessing treatment response. In this study, we retrospectively assessed volumetric changes of gray matter (GM) and white matter (WM) in glioma patients following photon irradiation using a heterogeneous MRI-dataset obtained in routine clinical practice at different sites with imaging parameters and magnetic field strengths. We found a significant reduction in WM volume at one year (p=0.01) and two years (p=0.008) post radio(chemo)therapy whereas corresponding GM volumes did not change significantly (p=0.05 and p=0.11, respectively). More importantly, we also found large variations in the segmented tissue volumes caused by the heterogeneous MR data, thus potentially masking more subtle tissue changes over time. On the basis of these observations, we present suggestions regarding data acquisitions in future prospective MR studies to assess such volumetric changes.