Multimodal Multimodal Magnetic Resonance Imaging Research Articles

Multimodal MRI and cognitive function in patients with breast cancer prior to adjuvant treatment — The role of fatigue

An increasing body of literature indicates that chemotherapy (ChT) for breast cancer (BC) is associated with adverse effects on the brain. Recent research suggests that cognitive and brain function in patients with BC may already be compromised before the start of chemotherapy. This is the first study combining neuropsychological testing, patient-reported outcomes, and multimodal magnetic resonance imaging (MRI) to examine pretreatment cognition and various aspects of brain function and structure in a large sample.Thirty-two patients with BC scheduled to receive ChT (pre-ChT+), 33 patients with BC not indicated to undergo ChT (pre-ChT−), and 38 no-cancer controls (NCs) were included. The examination consisted of a neuropsychological test battery, self-reported aspects of psychosocial functioning, and multimodal MRI.Patients with BC reported worse scores on several aspects of quality of life, such as higher levels of fatigue and stress. However, cortisol levels were not elevated in the patient groups compared to the control group. Overall cognitive performance was lower in the pre-ChT+ and the pre-ChT− groups compared to NC. Further, patients demonstrated prefrontal hyperactivation with increasing task difficulty on a planning task compared to NC, but not during a memory task. White matter integrity was lower in both patient groups. No differences in regional brain volume and brain metabolites were found. The cognitive and imaging data converged to show that symptoms of fatigue were associated with the observed abnormalities; the observed differences were no longer significant when fatigue was accounted for.This study suggests that cancer-related psychological or biological processes may adversely impact cognitive functioning and associated aspects of brain structure and function before the start of adjuvant treatment. Our findings stress the importance to further explore the processes underlying the expression of fatigue and to study whether it has a contributory role in subsequent treatment-related cognitive decline.

Multi-modal MRI of mild traumatic brain injury.

Multi-modal magnetic resonance imaging (MRI) that included high resolution structural imaging, diffusion tensor imaging (DTI), magnetization transfer ratio (MTR) imaging, and magnetic resonance spectroscopic imaging (MRSI) were performed in mild traumatic brain injury (mTBI) patients with negative computed tomographic scans and in an orthopedic-injured (OI) group without concomitant injury to the brain. The OI group served as a comparison group for mTBI. MRI scans were performed both in the acute phase of injury (~24 h) and at follow-up (~90 days). DTI data was analyzed using tract based spatial statistics (TBSS). Global and regional atrophies were calculated using tensor-based morphometry (TBM). MTR values were calculated using the standard method. MRSI was analyzed using LC Model. At the initial scan, the mean diffusivity (MD) was significantly higher in the mTBI cohort relative to the comparison group in several white matter (WM) regions that included internal capsule, external capsule, superior corona radiata, anterior corona radiata, posterior corona radiata, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major and forceps minor of the corpus callosum, superior longitudinal fasciculus, and corticospinal tract in the right hemisphere. TBSS analysis failed to detect significant differences in any DTI measures between the initial and follow-up scans either in the mTBI or OI group. No significant differences were found in MRSI, MTR or morphometry between the mTBI and OI cohorts either at the initial or follow-up scans with or without family wise error (FWE) correction. Our study suggests that a number of WM tracts are affected in mTBI in the acute phase of injury and that these changes disappear by 90 days. This study also suggests that none of the MRI-modalities used in this study, with the exception of DTI, is sensitive in detecting changes in the acute phase of mTBI.

Multimodal MRI as a diagnostic biomarker for amyotrophic lateral sclerosis.

ObjectiveReliable biomarkers for amyotrophic lateral sclerosis (ALS) are needed, given the clinical heterogeneity of the disease. Here, we provide proof-of-concept for using multimodal magnetic resonance imaging (MRI) as a diagnostic biomarker for ALS. Specifically, we evaluated the added diagnostic utility of proton magnetic resonance spectroscopy (MRS) to diffusion tensor imaging (DTI).MethodsTwenty-nine patients with ALS and 30 age- and gender-matched healthy controls underwent brain MRI which used proton MRS including spectral editing techniques to measure γ-aminobutyric acid (GABA) and DTI to measure fractional anisotropy of the corticospinal tract. Data were analyzed using logistic regression, t-tests, and generalized linear models with leave-one-out analysis to generate and compare the resulting receiver operating characteristic (ROC) curves.ResultsThe diagnostic accuracy is significantly improved when the MRS data were combined with the DTI data as compared to the DTI data only (area under the ROC curves (AUC) = 0.93 vs. AUC = 0.81; P = 0.05). The combined MRS and DTI data resulted in sensitivity of 0.93, specificity of 0.85, positive likelihood ratio of 6.20, and negative likelihood ratio of 0.08 whereas the DTI data only resulted in sensitivity of 0.86, specificity of 0.70, positive likelihood ratio of 2.87, and negative likelihood ratio of 0.20.InterpretationCombining multiple advanced neuroimaging modalities significantly improves disease discrimination between ALS patients and healthy controls. These results provide an important step toward advancing a multimodal MRI approach along the diagnostic test development pathway for ALS.

The Ins and Outs of the BCCAo Model for Chronic Hypoperfusion: A Multimodal and Longitudinal MRI Approach

Cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAo) in rodents has been proposed as an experimental model of white matter damage and vascular dementia. However, the histopathological and behavioral alterations reported in this model are variable and a full characterization of the dynamic alterations is not available. Here we implemented a longitudinal multimodal magnetic resonance imaging (MRI) design, including time-of-flight angiography, high resolution T1-weighted images, T2 relaxometry mapping, diffusion tensor imaging, and cerebral blood flow measurements up to 12 weeks after BCCAo or sham-operation in Wistar rats. Changes in MRI were related to behavioral performance in executive function tasks and histopathological alterations in the same animals. MRI frequently (70%) showed various degrees of acute ischemic lesions, ranging from very small to large subcortical infarctions. Independently, delayed MRI changes were also apparent. The patterns of MRI alterations were related to either ischemic necrosis or gliosis. Progressive microstructural changes revealed by diffusion tensor imaging in white matter were confirmed by observation of myelinated fiber degeneration, including severe optic tract degeneration. The latter interfered with the visually cued learning paradigms used to test executive functions. Independently of brain damage, BCCAo induced progressive arteriogenesis in the vertebrobasilar tree, a process that was associated with blood flow recovery after 12 weeks. The structural alterations found in the basilar artery were compatible with compensatory adaptive changes driven by shear stress. In summary, BCCAo in rats induces specific signatures in multimodal MRI that are compatible with various types of histological lesion and with marked adaptive arteriogenesis.

Multimodal magnetic resonance imaging for assessing lacunar infarction after proximal middle cerebral artery occlusion in a canine model

Background A new lacunar infarction model was recently established in beagle dogs through proximal middle cerebral artery (MCA) occlusion by thrombus. This study aimed to characterize the model by multimodal magnetic resonance imaging (MRI) and to investigate its potential role for the future stroke research. Methods The left proximal MCA was embolized with an autologous thrombus in six beagles. Diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) were performed every half hour during the first six hours after occlusion, followed by three time points at 12 hours, 24 hours, and one week. Perfusion-weighted imaging (PWI) and magnetic resonance angiography (MRA) were carried out at six hours, 24 hours and one week. The PWI-DWI mismatch ratio was defined as (PWI-DWI)/DWI ischemic volume. Results Lacunar infarcts induced by MCA occlusion were located in the left caudate nucleus and internal capsule. All the lesions could be detected within two hours by DWI. Lesion volume on DWI increased in a time dependent manner, from (87.19±67.16) mm3 at one hour up to (368.98±217.05) mm3 at 24 hours (P=0.009), while that on PWI gradually decreased from (7315.00±2054.38) mm3 at six hours to (4900.33±1319.71) mm3 at 24 hours and (3334.33±1195.11) mm3 at one week (P=0.002). The mismatch ratio was 41.93±22.75 at six hours after ischemia, showing “extensive mismatch”, and decreased to 18.10±13.74 at 24 hours (P=0.002). No MCA recanalization was observed within 24 hours after MCA occlusion. Conclusions Lacunar infarction induced by proximal MCA occlusion could be detected early by DWI and was characterized by extensive PWI-DWI mismatch. Multimodal MRI is useful to demonstrate the natural evolution of PWI-DWI mismatch. This ischemic model could be further used for investigating early thrombolysis in lacunar stroke showing extensive mismatch.

Pre- and Post-treatment with Cyclosporine a in a Rat Model of Transient Focal Cerebral Ischaemia with Multimodal MRI Screening

Irreversible damage may occur at reperfusion after sustained cerebral ischaemia. We investigated the value of cyclosporine A for reducing the infarct size in a model of transient middle cerebral artery occlusion. Twenty-seven Sprague-Dawley rats sustained a middle cerebral artery occlusion of one-hour. Acute multimodal Magnetic Resonance Imaging (MRI) was used during occlusion to confirm the success of surgery and measure baseline lesion size. Animals were randomly treated by: (i) intracarotid cyclosporine A (10 mg/kg) 20 mins before middle cerebral artery occlusion (pretreatment group); (ii) intracarotid cyclosporine A (10 mg/kg) immediately after reperfusion (post-treatment group); and (iii) intracarotid saline immediately after reperfusion. Histopathological measurements on day 1 showed a significant reduction of infarct size in the pretreatment group compared to the post-treatment (percentage values of ipsilateral hemispheres: 16 ± 5% vs. 29 ± 11%, P = 0·004) and saline groups (16 ± 5% vs. 42 ± 12%, P = 0·015). No significant difference was observed between the post-treatment and saline groups (P = 0·065). Behavioural examinations on day 1 showed no significant difference between groups. Immunohistochemistry showed a statistically significant reduction of microglial cell count in the pretreatment group compared to either saline or cyclosporine A post-treatment groups. We conclude that intracarotid cyclosporine A is effective in reducing infarct size when given prior to ischaemia, but not when administered at reperfusion.

Multimodal MRI Neuroimaging Biomarkers for Cognitive Normal Adults, Amnestic Mild Cognitive Impairment, and Alzheimer's Disease

Multimodal magnetic resonance imaging (MRI) techniques have been developed to noninvasively measure structural, metabolic, hemodynamic and functional changes of the brain. These advantages have made MRI an important tool to investigate neurodegenerative disorders, including diagnosis, disease progression monitoring, and treatment efficacy evaluation. This paper discusses recent findings of the multimodal MRI in the context of surrogate biomarkers for identifying the risk for AD in normal cognitive (NC) adults, brain anatomical and functional alterations in amnestic mild cognitive impairment (aMCI), and Alzheimer's disease (AD) patients. Further developments of these techniques and the establishment of promising neuroimaging biomarkers will enhance our ability to diagnose aMCI and AD in their early stages and improve the assessment of therapeutic efficacy in these diseases in future clinical trials.

Greater Default-Mode Network Abnormalities Compared to High Order Visual Processing Systems in Amnestic Mild Cognitive Impairment: An Integrated Multi-Modal MRI Study

We conducted an integrated multi-modal magnetic resonance imaging (MRI) study based on functional MRI (fMRI) data during a complex but cognitively preserved visual task in 15 amnestic mild cognitive impairment (a-MCI) patients and 15 Healthy Elders (HE). Independent Component Analysis of fMRI data identified a functional network containing an Activation Task Related Pattern (ATRP), including regions of the dorsal and ventral visual stream, and a Deactivation Task Related Pattern network (DTRP), with high spatial correspondence with the default-mode network (DMN). Gray matter (GM) volumes of the underlying ATRP and DTRP cortical areas were measured, and probabilistic tractography (based on diffusion MRI) identified fiber pathways within each functional network. For the ATRP network, a-MCI patients exhibited increased fMRI responses in inferior-ventral visual areas, possibly reflecting compensatory activations for more compromised dorsal regions. However, no significant GM or white matter group differences were observed within the ATRP network. For the DTRP/DMN, a-MCI showed deactivation deficits and reduced GM volumes in the posterior cingulate/precuneus, excessive deactivations in the inferior parietal lobe, and less fiber tract integrity in the cingulate bundles. Task performance correlated with DTRP-functionality in the HE group. Besides allowing the identification of functional reorganizations in the cortical network directly processing the task-stimuli, these findings highlight the importance of conducting integrated multi-modal MRI studies in MCI based on spared cognitive domains in order to identify functional abnormalities in critical areas of the DMN and their precise anatomical substrates. These latter findings may reflect early neuroimaging biomarkers in dementia.

Lamotrigine suppresses neurophysiological responses to somatosensory stimulation in the rodent

Neurotransmitter release and voltage-gated ion channel activity in excitatory neurons are critical for understanding and interpreting neuroimaging signals. Couplings between changes in neural activity and energetic/vascular responses are assumed for interpretation of neuroimaging signals. To investigate involvement of neural events to neuroenergetic/neurovascular responses, we conducted multi-modal magnetic resonance imaging (MRI) measurements (at 7.0 T) and electrophysiological recordings (with high impedance microelectrodes) for local field potential (LFP) and spiking frequency ( ν) in α-chloralose-anesthetized rats. The rats underwent forepaw stimulation before and after treatment of lamotrigine, a neuronal voltage-gated ion channel blocker and glutamate release inhibitor. Multi-modal MRI measurements of cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) signal were combined to estimate changes in cerebral metabolic rate of oxygen consumption (CMRo 2). Lamotrigine did not appreciably affect values of ν, CBF, and CMRo 2 in the resting state. After lamotrigine treatment, evoked changes in LFP and ν were attenuated, which were consistent with commensurate declines in ΔCBF and ΔCMRo 2. While number of evoked BOLD-activated voxels was considerably reduced with lamotrigine, intensities of voxels in middle cortical layers were affected to a lesser degree by lamotrigine. The results suggest that lamotrigine suppresses evoked neurophysiological (i.e., neural/energetic/vascular) responses, both in terms of volume of tissue activated and degree of activation in the foci. Since lamotrigine affects evoked responses but not the basal signals, it can be suggested that glutamate release and activity of voltage-gated ion channels are essential for initiating evoked energetic/vascular responses, and thereby important for interpretation of incremental changes in neuroimaging signal.