OBJECTIVE: To investigate the relationship between white matter abnormalities and impairment of gait and balance in older persons. METHODS: Quantitative MRI was used to evaluate the brain tissue compartments of 28 older individuals separated into normal and impaired groups on the basis of mobility performance testing using the Short Physical Performance Battery. In addition, individuals were tested on six indices of gait and balance. For imaging data, segmentation of intracranial volume into four tissue classes was performed using template-driven segmentation, in which signal-intensity-based statistical tissue classification is refined using a digital brain atlas as anatomic template. RESULTS: Both decreased white matter volume, which was age-related, and increased white matter signal abnormalities, which were not age-related, were observed in the mobility-impaired group compared with the control subjects. The average volume of white matter signal abnormalities for impaired individuals was nearly double that of control subjects. CONCLUSIONS: This cross-sectional study suggests that decreased white matter volume is age-related, whereas increased white matter signal abnormalities are most likely to occur as a result of disease. Both of these changes are independently associated with impaired mobility in older persons and therefore likely to be additive factors of motor disability.
The goal of the Image Guided Therapy Program, as the name implies, is to develop the use of imaging to guide minimally invasive therapy. The program combines interventional and intraoperative magnetic resonance imaging (MRI) with high-performance computing and novel therapeutic devices. In clinical practice the multidisciplinary program provides for the investigation of a wide range of interventional and surgical procedures. The Signa SP 0.5 T superconducting MRI system (GE Medical Systems, Milwaukee, WI) has a 56-cm-wide vertical gap, allowing access to the patient and permitting the execution of interactive MRI-guided procedures. This system is integrated with an optical tracking system and utilizes flexible surface coils and MRI-compatible displays to facilitate procedures. Images are obtained with routine pulse sequences. Nearly real-time imaging, with fast gradient-recalled echo sequences, may be acquired at a rate of one image every 1.5 s with interactive image plane selection. Since 1994, more than 800 of these procedures, including various percutaneous procedures and open surgeries, have been successfully performed at Brigham and Women's Hospital (Boston, MA).
A novel image segmentation algorithm was developed to allow the automatic segmentation of both normal and abnormal anatomy from medical images. The new algorithm is a form of spatially varying statistical classification, in which an explicit anatomical template is used to moderate the segmentation obtained by statistical classification. The algorithm consists of an iterated sequence of spatially varying classification and nonlinear registration, which forms an adaptive, template moderated (ATM), spatially varying statistical classification (SVC). Classification methods and nonlinear registration methods are often complementary, both in the tasks where they succeed and in the tasks where they fail. By integrating these approaches the new algorithm avoids many of the disadvantages of each approach alone while exploiting the combination. The ATM SVC algorithm was applied to several segmentation problems, involving different image contrast mechanisms and different locations in the body. Segmentation and validation experiments were carried out for problems involving the quantification of normal anatomy (MRI of brains of neonates) and pathology of various types (MRI of patients with multiple sclerosis, MRI of patients with brain tumors, MRI of patients with damaged knee cartilage). In each case, the ATM SVC algorithm provided a better segmentation than statistical classification or elastic matching alone.
Computer-assisted 3D planning, navigation and the possibilities offered by intra-operative imaging updates have made a large impact on neurological surgery. Three-dimensional rendering of complex medical image information, as well as co-registration of multimodal sources has reached a highly sophisticated level. When introduced into surgical navigation however, this pre-operative data is unable to account for intra-operative changes, ('brain-shift'). To update structural information during surgery, an open-configured, intra-operative MRI (Signa SP, 0.5 T) was realised at our institution in 1995. The design, advantages, limitations and current applications of this system are discussed, with emphasis on the integration of imaging into procedures. We also introduce our integrated platform for intra-operative visualisation and navigation, the 3D Slicer.
OBJECTIVE: Recent evidence suggests that the cerebellum may play a role in higher cognitive functions and, therefore, may play an important role in schizophrenia. METHOD: The authors used magnetic resonance imaging to measure cerebellum and vermis volume in 15 patients with schizophrenia and 15 normal comparison subjects. RESULTS: They found that 1) vermis volume was greater in patients with schizophrenia than in normal subjects, 2) greater vermis white matter volume in the patients with schizophrenia significantly correlated with severity of positive symptoms and thought disorder and with impairment in verbal logical memory, and 3) patients with schizophrenia showed a trend for more cerebellar hemispheric volume asymmetry (left greater than right). CONCLUSIONS: These data suggest that an abnormality in the vermis may contribute to the pathophysiology of schizophrenia.
OBJECTIVE: Gray matter volume and glucose utilization have been reported to be reduced in the left subgenual cingulate of subjects with familial bipolar or unipolar depression. It is unclear whether these findings are secondary to recurrent illness or are part of a familial/genetic syndrome. The authors' goal was to clarify these findings. METHOD: Volumetric analyses were performed by using magnetic resonance imaging in 41 patients experiencing their first episode of affective disorder or schizophrenia and in 20 normal comparison subjects. RESULTS: The left subgenual cingulate volume of the patients with affective disorder who had a family history of affective disorder was smaller than that of patients with affective disorder with no family history of the illness and the normal comparison subjects. Patients with schizophrenia did not differ from comparison subjects in left subgenual cingulate volume. CONCLUSIONS: Left subgenual cingulate abnormalities are present at first hospitalization for psychotic affective disorder in patients who have a family history of affective disorder.
BACKGROUND: Structural MRI data indicate schizophrenics have reduced left-sided temporal lobe gray matter volumes, especially in the superior temporal gyrus (STG) and medial temporal lobe. Our data further suggest a specificity to schizophrenia spectrum disorders of STG volume reduction. Interpretation of research studies involving schizophrenics may be complicated by the effects of exposure to neuroleptics and chronic illness. Sharing the same genetic diathesis of schizophrenics, subjects with schizotypal personality disorder (SPD) offer a unique opportunity to evaluate commonalities between schizophrenia and SPD, particularly as SPD subjects are characterized by cognitive and perceptual distortions, an inability to tolerate close friendships, and odd behavior, but they are not psychotic and so have generally not been prescribed neuroleptics nor hospitalized. Evaluation of brain structure in SPD may thus offer insight into the "endophenotype" common to both disorders. In addition, differences between groups may suggest which are the brain structures of schizophrenics that contribute to the development of psychosis. METHODS: To test the hypothesis of whether SPD subjects might show similar STG abnormalities, STG and medial temporal lobe regions of interest (ROI) were manually drawn on high resolution coronal MRI 1.5 mm thick slices. Images were derived from 16 right-handed male SPD subjects, without regard to family history, and 14 healthy, right-handed, comparison males who did not differ from the SPD group on parental socio-economic status, age, or verbal IQ. RESULTS: As predicted, SPD subjects showed a reduction in left STG gray matter volume compared with age and gender matched comparison subjects. SPD subjects also showed reduced parahippocampal left/right asymmetry and a high degree of disordered thinking. Comparisons with chronic schizophrenics previously studied by us showed the SPD group had a similarity of left STG gray matter volume reduction, but fewer medial temporal lobe abnormalities. CONCLUSIONS: These abnormalities strengthen the hypothesis of a temporal lobe abnormality in SPD, and the similarity of STG findings in schizophrenia and SPD suggest that STG abnormalities may be part of the spectrum "endophenotype." It is also possible that presence of medial temporal lobe abnormalities may help to differentiate who will develop schizophrenia and who will develop the less severe schizophrenia spectrum disorder, SPD.
PURPOSE: To review preliminary experience with an open-bore magnetic resonance (MR) imaging system for guidance in intracranial surgical procedures. MATERIALS AND METHODS: A vertically oriented, open-configuration 0.5-T MR imager was housed in a sterile procedure room. Receive and transmit surface coils were wrapped around the patient's head, and images were displayed on monitors mounted in the gap of the magnet and visible to surgeons. During 2 years, 200 intracranial procedures were performed. RESULTS: There were 111 craniotomies, 68 biopsies, 12 intracranial cyst evaluations, four subdural drainages, and five transsphenoidal pituitary resections performed with the intraoperative MR unit. In each case, the intraoperative MR system yielded satisfactory results by allowing the radiologist to guide surgeons toward lesions and to assist in treatment. In two patients, hyperacute hemorrhage was noted and removed. The duration of the procedure and the complication rate were similar to those of conventional surgery. CONCLUSION: Intraoperative MR imaging was successfully implemented for a variety of intracranial procedures and provided continuous visual feedback, which can be helpful in all stages of neurosurgical intervention without affecting the duration of the procedure or the incidence of complications. This system has potential advantages over conventional frame-based and frameless stereotactic procedures with respect to the safety and effectiveness of neurosurgical interventions.
OBJECTIVE: Studies of schizophrenia have not clearly defined handedness as a differentiating variable. Moreover, the relationship between thought disorder and anatomical anomalies has not been studied extensively in left-handed schizophrenic men. The twofold purpose of this study was to investigate gray matter volumes in the superior temporal gyrus of the temporal lobe (left and right hemispheres) in left-handed schizophrenic men and left-handed comparison men, in order to determine whether thought disorder in the left-handed schizophrenic men correlated with tissue volume abnormalities. METHOD: Left-handed male patients (N = 8) with DSM-III-R diagnoses of schizophrenia were compared with left-handed comparison men (N = 10) matched for age, socioeconomic status, and IQ. Magnetic resonance imaging (MRI) with a 1.5-T magnet was used to obtain scans, which consisted of contiguous 1.5-mm slices of the whole brain. MRI analyses (as previously defined by the authors) included the anterior, posterior, and total superior temporal gyrus in both the left and right hemispheres. RESULTS: There were three significant findings regarding the left-handed schizophrenic men: 1) bilaterally smaller gray matter volumes in the posterior superior temporal gyrus (16% smaller on the right, 15% smaller on the left); 2) a smaller volume on the right side of the total superior temporal gyrus; and 3) a positive correlation between thought disorder and tissue volume in the right anterior superior temporal gyrus. CONCLUSIONS: These results suggest that expression of brain pathology differs between left-handed and right-handed schizophrenic men and that the pathology is related to cognitive disturbance.
Karl-Heinz Nenning, Julia Furtner, Barbara Kiesel, Ernst Schwartz, Thomas Roetzer, Nikolaus Fortelny, Christoph Bock, Anna Grisold, Martha Marko, Fritz Leutmezer, Hesheng Liu, Polina Golland, Sophia Stoecklein, Johannes A Hainfellner, Gregor Kasprian, Daniela Prayer, Christine Marosi, Georg Widhalm, Adelheid Woehrer, and Georg Langs. 10/2020. “Distributed Changes of the Functional Connectome in Patients with Glioblastoma.” Sci Rep, 10, 1, Pp. 18312.Abstract
Glioblastoma might have widespread effects on the neural organization and cognitive function, and even focal lesions may be associated with distributed functional alterations. However, functional changes do not necessarily follow obvious anatomical patterns and the current understanding of this interrelation is limited. In this study, we used resting-state functional magnetic resonance imaging to evaluate changes in global functional connectivity patterns in 15 patients with glioblastoma. For six patients we followed longitudinal trajectories of their functional connectome and structural tumour evolution using bi-monthly follow-up scans throughout treatment and disease progression. In all patients, unilateral tumour lesions were associated with inter-hemispherically symmetric network alterations, and functional proximity of tumour location was stronger linked to distributed network deterioration than anatomical distance. In the longitudinal subcohort of six patients, we observed patterns of network alterations with initial transient deterioration followed by recovery at first follow-up, and local network deterioration to precede structural tumour recurrence by two months. In summary, the impact of focal glioblastoma lesions on the functional connectome is global and linked to functional proximity rather than anatomical distance to tumour regions. Our findings further suggest a relevance for functional network trajectories as a possible means supporting early detection of tumour recurrence.
Using positron emission tomography, we recently demonstrated elevated brain levels of the 18kDa translocator protein (TSPO), a glial activation marker, in chronic low back pain (cLBP) patients, compared to healthy controls (HC). Here, we first sought to replicate the original findings in an independent cohort (15 cLBP, 37.8±12.5 y/o; 18 HC, 48.2±12.8 y/o). We then trained random forest (RF) machine learning algorithms based on TSPO imaging features combining discovery and replication cohorts (totaling 25 cLBP, 42.4±13.2 y/o; 27 HC, 48.9±12.6 y/o), in order to explore whether image features other than the mean contain meaningful information that might contribute to the discrimination of cLBP patients and HC. Feature importance was ranked usind SHapley Additive exPlanations (SHAP) values, and the classification performance (in terms of AUC values) of classifiers containing only the mean, other features, or all features was compared using the DeLong test. Both region-of-interest (ROI) and voxelwise analyses replicated the original observation of thalamic TSPO signal elevations in cLBP patients compared to HC (p's<0.05). The RF-based analyses revealed that while the mean is a discriminating feature, other features demonstrate similar level of importance, including the maximum, kurtosis and entropy.Our observations suggest that thalamic neuroinflammatory signal is a reproducible and discriminating feature for cLBP, further supporting a role for glial activation in human chronic low back pain, and the exploration of neuroinflammation as a therapeutic target for chronic pain. This work further shows that TSPO signal contains a richness of information that the simple mean might fail to capture completely.
BACKGROUND: Extracellular free water within cerebral white matter tissue has been shown to increase with age and pathology, yet the cognitive consequences of free water in typical aging prior to the development of neurodegenerative disease remains unclear. Understanding the contribution of free water to cognitive function in older adults may provide important insight into the neural mechanisms of the cognitive aging process. METHODS: A diffusion-weighted MRI measure of extracellular free water as well as a commonly used diffusion MRI metric (fractional anisotropy) along nine bilateral white matter pathways were examined for their relationship with cognitive function assessed by the NIH Toolbox Cognitive Battery in 47 older adults (mean age = 74.4 years, SD = 5.4 years, range = 65-85 years). Probabilistic tractography at the 99th percentile level of probability (Tracts Constrained by Underlying Anatomy; TRACULA) was utilized to produce the pathways on which microstructural characteristics were overlaid and examined for their contribution to cognitive function independent of age, education, and gender. RESULTS: When examining the 99th percentile probability core white matter pathway derived from TRACULA, poorer fluid cognitive ability was related to higher mean free water values across the angular and cingulum bundles of the cingulate gyrus, as well as the corticospinal tract and the superior longitudinal fasciculus. There was no relationship between cognition and mean FA or free water-adjusted FA across the 99th percentile core white matter pathway. Crystallized cognitive ability was not associated with any of the diffusion measures. When examining cognitive domains comprising the NIH Toolbox Fluid Cognition index relationships with these white matter pathways, mean free water demonstrated strong hemispheric and functional specificity for cognitive performance, whereas mean FA was not related to age or cognition across the 99th percentile pathway. CONCLUSIONS: Extracellular free water within white matter appears to increase with normal aging, and higher values are associated with significantly lower fluid but not crystallized cognitive functions. When using TRACULA to estimate the core of a white matter pathway, a higher degree of free water appears to be highly specific to the pathways associated with memory, working memory, and speeded decision-making performance, whereas no such relationship existed with FA. These data suggest that free water may play an important role in the cognitive aging process, and may serve as a stronger and more specific indicator of early cognitive decline than traditional diffusion MRI measures, such as FA.
PURPOSE: To optimize diffusion-relaxation MRI with tensor-valued diffusion encoding for precise estimation of compartment-specific fractions, diffusivities, and T values within a two-compartment model of white matter, and to explore the approach in vivo. METHODS: Sampling protocols featuring different b-values (b), b-tensor shapes (b ), and echo times (TE) were optimized using Cramér-Rao lower bounds (CRLB). Whole-brain data were acquired in children, adults, and elderly with white matter lesions. Compartment fractions, diffusivities, and T values were estimated in a model featuring two microstructural compartments represented by a "stick" and a "zeppelin." RESULTS: Precise parameter estimates were enabled by sampling protocols featuring seven or more "shells" with unique b/b /TE-combinations. Acquisition times were approximately 15 minutes. In white matter of adults, the "stick" compartment had a fraction of approximately 0.5 and, compared with the "zeppelin" compartment, featured lower isotropic diffusivities (0.6 vs. 1.3 μm /ms) but higher T values (85 vs. 65 ms). Children featured lower "stick" fractions (0.4). White matter lesions exhibited high "zeppelin" isotropic diffusivities (1.7 μm /ms) and T values (150 ms). CONCLUSIONS: Diffusion-relaxation MRI with tensor-valued diffusion encoding expands the set of microstructure parameters that can be precisely estimated and therefore increases their specificity to biological quantities.
The corticospinal tract (CST) is one of the most well studied tracts in human neuroanatomy. Its clinical significance can be demonstrated in many notable traumatic conditions and diseases such as stroke, spinal cord injury (SCI) or amyotrophic lateral sclerosis (ALS). With the advent of diffusion MRI and tractography the computational representation of the human CST in a 3D model became available. However, the representation of the entire CST and, specifically, the hand motor area has remained elusive. In this paper we propose a novel method, using manually drawn ROIs based on robustly identifiable neuroanatomic structures to delineate the entire CST and isolate its hand motor representation as well as to estimate their variability and generate a database of their volume, length and biophysical parameters. Using 37 healthy human subjects we performed a qualitative and quantitative analysis of the CST and the hand-related motor fiber tracts (HMFTs). Finally, we have created variability heat maps from 37 subjects for both the aforementioned tracts, which could be utilized as a reference for future studies with clinical focus to explore neuropathology in both trauma and disease states.