Diffusion Tensor Imaging Magnetic Resonance Imaging Research Articles

The role of imaging in diagnosing and managing tendinopathy

Tendons were first imaged in the late 1980’s, where it was apparent that tendon pathology was highly associated with tendon pain, normal tendons on imaging almost never gave rise to symptoms. As larger cohorts were imaged in the early 2000’s it became apparent that tendon pathology existed in tendons that were not currently symptomatic, and that never developed symptoms. This questioned the role of imaging in diagnosing the tendon as the source of pain, as there are no imaging criteria that indicate if the tendon is painful. Pathology of imaging is also not predictive of symptoms, again there is no indication on imaging to determine the likelihood of a tendon becoming symptomatic. Degenerative tendon pathology does not heal, so serial imaging of tendon during rehabilitation will indicate little or no change, often despite improvements in pain and function. The role of imaging in the management if tendon pathology is limited to diagnosis the early stage of pathology (reactive tendon pathology) where strategies to decrease load are best practice. Ultrasound imaging provides the best clinical information about tendons, as it can indicate tendon fascicle continuity, the level of vascularity and an indication or proteoglycan infiltration. Magnetic resonance imaging (MRI) can also indicate levels of proteoglycan and vascular infiltration but with less clarity. Currently, neither of these modalities improve clinical diagnosis and amnagement, and are limited in providing a differential diagniosis of pain. Newer outputs from ultrasound such as elastography, as well as enhanced ultrasound imaging (ultrasound tissue characterisation) and specialised sequences on MRI (diffusion tensor imaging, ultrashort echo time) may improve clinical diagnosis and prognosis, however the inability of the tendon to heal and the inability of imaging to diagnose pain suggest that tendons will remain and enigma to imaging in the short to long term.

Single-subject classification of presymptomatic frontotemporal dementia mutation carriers using multimodal MRI.

BackgroundClassification models based on magnetic resonance imaging (MRI) may aid early diagnosis of frontotemporal dementia (FTD) but have only been applied in established FTD cases. Detection of FTD patients in earlier disease stages, such as presymptomatic mutation carriers, may further advance early diagnosis and treatment. In this study, we aim to distinguish presymptomatic FTD mutation carriers from controls on an individual level using multimodal MRI-based classification.MethodsAnatomical MRI, diffusion tensor imaging (DTI) and resting-state functional MRI data were collected in 55 presymptomatic FTD mutation carriers (8 microtubule-associated protein Tau, 35 progranulin, and 12 chromosome 9 open reading frame 72) and 48 familial controls. We calculated grey and white matter density features from anatomical MRI scans, diffusivity features from DTI, and functional connectivity features from resting-state functional MRI. These features were applied in a recently introduced multimodal behavioural variant FTD (bvFTD) classification model, and were subsequently used to train and test unimodal and multimodal carrier-control models. Classification performance was quantified using area under the receiver operator characteristic curves (AUC).ResultsThe bvFTD model was not able to separate presymptomatic carriers from controls beyond chance level (AUC = 0.582, p = 0.078). In contrast, one unimodal and several multimodal carrier-control models performed significantly better than chance level. The unimodal model included the radial diffusivity feature and had an AUC of 0.642 (p = 0.032). The best multimodal model combined radial diffusivity and white matter density features (AUC = 0.684, p = 0.004).ConclusionsFTD mutation carriers can be separated from controls with a modest AUC even before symptom-onset, using a newly created carrier-control classification model, while this was not possible using a recent bvFTD classification model. A multimodal MRI-based classification score may therefore be a useful biomarker to aid earlier FTD diagnosis. The exclusive selection of white matter features in the best performing model suggests that the earliest FTD-related pathological processes occur in white matter.

Whole Brain White Matter Microstructure and Upper Limb Function: Longitudinal Changes in Fractional Anisotropy and Axial Diffusivity in Post-Stroke Patients.

Background:Diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) measuring fractional anisotropy (FA) and axial diffusivity (AD) may be a useful biomarker for monitoring changes in white matter after stroke, but its associations with upper-limb motor recovery have not been well studied. We aim to describe changes in the whole-brain FA and AD in five post-stroke patients in relation to kinematic measures of elbow flexion to better understand the relationship between FA and AD changes and clinico-kinematic measures of upper limb motor recovery.Methods:We performed DTI MRI at two timepoints during the acute phase of stroke, measuring FA and AD across 48 different white matter tract regions in the brains of five hemiparetic patients with infarcts in the cortex, pons, basal ganglia, thalamus, and corona radiata. We tracked the progress of these patients using clinical Fugl-Meyer Assessments and kinematic measures of elbow flexion at the acute phase within 14 (mean: 9.4 ± 2.49) days of stroke symptom onset and at a follow-up appointment 2 weeks later (mean: 16 ± 1.54) days.Results:Changes in FA and AD in 48 brain regions occurring during stroke rehabilitation are described in relation to motor recovery. In this case series, one patient with a hemipontine infarct showed an increase in FA of the ipsilateral and contralateral corticospinal tract, whereas other patients with lesions involving the corona radiata and middle cerebral artery showed widespread decreases in perilesional FA. On the whole, FA and AD seemed to behave inversely to each other.Conclusions:This case series describes longitudinal changes in perilesional and remote FA and AD in relation to kinematic parameters of elbow flexion at the subacute post-stroke period. Although studies with larger sample sizes are needed, our findings indicate that longitudinally measured changes in DTI-based measurements of white matter microstructural integrity may aid in the prognostication of patients affected by motor stroke.

Alcohol use effects on adolescent brain development revealed by simultaneously removing confounding factors, identifying morphometric patterns, and classifying individuals

Group analysis of brain magnetic resonance imaging (MRI) metrics frequently employs generalized additive models (GAM) to remove contributions of confounding factors before identifying cohort specific characteristics. For example, the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) used such an approach to identify effects of alcohol misuse on the developing brain. Here, we hypothesized that considering confounding factors before group analysis removes information relevant for distinguishing adolescents with drinking history from those without. To test this hypothesis, we introduce a machine-learning model that identifies cohort-specific, neuromorphometric patterns by simultaneously training a GAM and generic classifier on macrostructural MRI and microstructural diffusion tensor imaging (DTI) metrics and compare it to more traditional group analysis and machine-learning approaches. Using a baseline NCANDA MR dataset (N = 705), the proposed machine learning approach identified a pattern of eight brain regions unique to adolescents who misuse alcohol. Classifying high-drinking adolescents was more accurate with that pattern than using regions identified with alternative approaches. The findings of the joint model approach thus were (1) impartial to confounding factors; (2) relevant to drinking behaviors; and (3) in concurrence with the alcohol literature.

Voxel-based automated detection of focal cortical dysplasia lesions using diffusion tensor imaging and T2-weighted MRI data

The aim of this study was to automatically detect focal cortical dysplasia (FCD) lesions in patients with extratemporal lobe epilepsy by relying on diffusion tensor imaging (DTI) and T2-weighted magnetic resonance imaging (MRI) data. We implemented an automated classifier using voxel-based multimodal features to identify gray and white matter abnormalities of FCD in patient cohorts. In addition to the commonly used T2-weighted image intensity feature, DTI-based features were also utilized. A Gaussian processes for machine learning (GPML) classifier was tested on 12 patients with FCD (8 with histologically confirmed FCD) scanned at 1.5 T and cross-validated using a leave-one-out strategy. Moreover, we compared the multimodal GPML paradigm's performance with that of single modal GPML and classical support vector machine (SVM). Our results demonstrated that the GPML performance on DTI-based features (mean AUC = 0.63) matches with the GPML performance on T2-weighted image intensity feature (mean AUC = 0.64). More promisingly, GPML yielded significantly improved performance (mean AUC = 0.76) when applying DTI-based features to multimodal paradigm. Based on the results, it can also be clearly stated that the proposed GPML strategy performed better and is robust to unbalanced dataset contrary to SVM that performed poorly (AUC = 0.69). Therefore, the GPML paradigm using multimodal MRI data containing DTI modality has promising result towards detection of the FCD lesions and provides an effective direction for future researches.

Gliovascular changes precede white matter damage and long-term disorders in juvenile mild closed head injury.

Traumatic brain injury (TBI) is a leading cause of hospital visits in pediatric patients and often leads to long-term disorders even in cases of mild severity. White matter (WM) alterations are commonly observed in patients months or years after the injury assessed by magnetic resonance imaging (MRI), but little is known about WM pathophysiology early after mild pediatric TBI. To evaluate the status of the gliovascular unit in this context, mild TBI was induced in postnatal-day 17 mice using a closed head injury model with two grades of severity (G1, G2). G2 resulted in significant WM edema (increased T2-signal) and BBB damage (IgG-extravasation immunostaining) whereas decreased T2 and the increased levels of astrocytic water-channel AQP4 were observed in G1 mice 1 day post-injury. Both severities induced astrogliosis (GFAP immunolabeling). No changes in myelin and neurofilament were detected at this acute time point. One month after injury G2 mice exhibited diffusion tensor imaging MRI alterations (decreased fractional anisotropy) accompanied by decreased neurofilament staining in the WM. Both severities induced behavioral impairments at this time point. In conclusion, long-term deficits and WM changes similar to those found after clinical TBI are preceded by distinct early gliovascular phenotype alterations after juvenile mild TBI, revealing AQP4 as a potential candidate for severity-based treatments.

T2 , T1ρ and TRAFF4 detect early regenerative changes in mouse ischemic skeletal muscle.

The identification of areas with regenerative potential in ischemic tissues would allow the targeting of treatments supporting tissue recovery. The regeneration process involves the activation of several cellular and molecular responses which could be detected using magnetic resonance imaging (MRI). However, to date, magnetic resonance (MR) relaxation parameters have received little attention in the diagnosis and follow-up of limb ischemia. The purpose of this study was to evaluate the feasibility of different MRI relaxation and diffusion tensor imaging parameters in the detection of areas showing early signs of regeneration in ischemic mouse skeletal muscles. T2 and T1ρ relaxation time constants, together with TRAFFn , T1 and diffusion tensor imaging, were evaluated to differentiate areas of regeneration in a mouse hind limb ischemia model before and 0, 1, 4, 7, 14 and 30days after ischemia. All the measured relaxation times were longer in the areas of early regeneration compared with normal muscle tissue. The relaxation times increased after ischemia in the ischemic muscles, reaching a maximum at 4-7days after occlusion, coinciding with the appearance of early signs of regeneration. Fractional anisotropy decreased significantly (p < 0.05) on days 1-4, whereas mean diffusivity, λ1 and λ2 decreased later, starting at day 7 after ischemia compared with the pre-operational time point. The percentages of areas with different tissue morphologies were determined based on histological analysis of the ischemic muscle cross-sections, and correlations between the percentages obtained and different relaxation times were calculated. The highest correlation between relaxation times and histology was achieved with T2 , T1ρ and TRAFF4 (R2 = 0.96, R2 = 0.92 and R2 = 0.84, respectively, p < 0.01). Early regenerative changes were visible using T2 , T1ρ and TRAFF4 MR relaxation time constants in skeletal muscle after ischemia. These markers could potentially be used for the identification of targets for therapies supporting muscle regeneration after ischemic injury.

Imaging Pediatric Multiple Sclerosis-Challenges and Recent Advances.

Pediatric onset multiple sclerosis (POMS) is a rare disease with an incidence of 0.07 to 2.9/100'000 children per year. It follows a relapsing-remitting disease course and is characterized by rapid accrual of inflammatory lesions, high relapse frequency, and early cognitive impairment. Magnetic resonance imaging (MRI) plays a pivotal role in the diagnosis of POMS, and in the exclusion of other disorders mimicking POMS. Furthermore, MRI aids in disease monitoring, and in the evaluation of therapeutic efficacy in both clinical practice and clinical trials. Volumetric MRI studies, diffusion tensor imaging, resting-state, and task-based functional MRI provide deeper insight into the impact of POMS on maturing neural networks. This review article aims to highlight the importance of MRI in the care of POMS patients and to provide an overview on the different MRI techniques used in the management of POMS.

Altered Connectivity of the Anterior Cingulate and the Posterior Superior Temporal Gyrus in a Longitudinal Study of Later-life Depression.

Patients with later-life depression (LLD) show abnormal gray matter (GM) volume, white matter (WM) integrity and functional connectivity in the anterior cingulate cortex (ACC) and posterior superior temporal gyrus (pSTG), but it remains unclear whether these abnormalities persist over time. We examined whether structural and functional abnormalities in these two regions are present within the same subjects during depressed vs. remitted phases. Sixteen patients with LLD and 30 healthy subjects were studied over a period of 1.5 years. Brain images obtained with a 3-Tesla magnetic resonance imaging (MRI) system were analyzed by voxel-based morphometry of the GM volume, and diffusion tensor imaging (DTI) and resting-state functional MRI were used to assess ACC–pSTG connectivity. Patients with LLD in the depressed and remitted phases showed significantly smaller GM volume in the left ACC and left pSTG than healthy subjects. Both patients with LLD in the depressed and remitted phases had significantly higher diffusivities in the WM tract of the left ACC–pSTG than healthy subjects. Remitted patients with LLD showed lower functional ACC–pSTG connectivity compared to healthy subjects. No difference was found in the two regions between depressed and remitted patients in GM volume, structural or functional connectivity. Functional ACC–pSTG connectivity was positively correlated with lower global function during remission. Our preliminary data show that structural and functional abnormalities of the ACC and pSTG occur during LLD remission. Our findings tentatively reveal the brain pathophysiology involved in LLD and may aid in developing neuroanatomical biomarkers for this condition.

Diffusion tensor imaging MRI of sickle cell kidney disease: initial results and comparison with iron deposition

Chronic kidney disease (CKD) occurs in over one-third of patients with sickle cell disease (SCD) and can progress to end-stage renal disease. Unfortunately, current clinical assessments of kidney function are insensitive to early-stage CKD. Previous studies have shown that diffusion magnetic resonance imaging (MRI) can sensitively detect regional renal microstructural changes associated with early-stage CKD. However, previous MRI studies in patients with SCD have been largely limited to the detection of renal iron deposition assessed by T2 * relaxometry. In this pilot imaging study, we compare MRI assessments of renal microstructure (diffusion) and iron deposition (T2 *) in patients with SCD and in non-SCD control subjects. Diffusion tensor imaging (DTI) and T2 * relaxometry MRI data were obtained for pediatric (n = 5) and adult (n = 4) patients with SCD, as well as for non-SCD control subjects (n = 10), on a Siemens Espree 1.5-T MRI scanner. A region-of-interest analysis was used to calculate mean medullary and cortical values for each MRI metric. MRI findings were also compared with clinical assessments of renal function and hemolysis. Patients with SCD showed a significant decrease in medullary fractional anisotropy (FA, p = 0.0001) in comparison with non-SCD subjects, indicative of microstructural alterations in the renal medulla of patients with SCD. Cortical and medullary reductions in T2 * (increased iron deposition, p = ≤0.0001) were also observed. Significant correlations were also observed between kidney T2 * assessments and multiple measures of hemolysis. This is the first DTI MRI study of patients with SCD to demonstrate reductions in medullary FA despite no overt CKD [estimated glomerular filtration rate (eGFR) > 100mL/min/1.73m2 ]. These medullary FA changes are consistent with previous studies in patients with CKD, and suggest that DTI MRI can provide a useful measure of kidney injury to complement MRI assessments of iron deposition.

Single-subject classification of presymptomatic frontotemporal dementia mutation carriers using multimodal MRI.

BackgroundClassification models based on magnetic resonance imaging (MRI) may aid early diagnosis of frontotemporal dementia (FTD) but have only been applied in established FTD cases. Detection of FTD patients in earlier disease stages, such as presymptomatic mutation carriers, may further advance early diagnosis and treatment. In this study, we aim to distinguish presymptomatic FTD mutation carriers from controls on an individual level using multimodal MRI-based classification.MethodsAnatomical MRI, diffusion tensor imaging (DTI) and resting-state functional MRI data were collected in 55 presymptomatic FTD mutation carriers (8 microtubule-associated protein Tau, 35 progranulin, and 12 chromosome 9 open reading frame 72) and 48 familial controls. We calculated grey and white matter density features from anatomical MRI scans, diffusivity features from DTI, and functional connectivity features from resting-state functional MRI. These features were applied in a recently introduced multimodal behavioural variant FTD (bvFTD) classification model, and were subsequently used to train and test unimodal and multimodal carrier-control models. Classification performance was quantified using area under the receiver operator characteristic curves (AUC).ResultsThe bvFTD model was not able to separate presymptomatic carriers from controls beyond chance level (AUC = 0.570, p = 0.11). In contrast, one unimodal and several multimodal carrier-control models performed significantly better than chance level. The unimodal model included the radial diffusivity feature and had an AUC of 0.646 (p = 0.021). The best multimodal model combined radial diffusivity and white matter density features (AUC = 0.680, p = 0.005).ConclusionsFTD mutation carriers can be separated from controls with a modest AUC even before symptom-onset, using a newly created carrier-control classification model, while this was not possible using a recent bvFTD classification model. A multimodal MRI-based classification score may therefore be a useful biomarker to aid earlier FTD diagnosis. The exclusive selection of white matter features in the best performing model suggests that the earliest FTD-related pathological processes occur in white matter.

The Role of Magnetic Resonance Imaging–Diffusion Tensor Imaging in Predicting Pain Related to Endometriosis: A Preliminary Study

ObjectivesTo evaluate the sacral nerve root features by the means of magnetic resonance imaging–diffusion tensor imaging (MRI-DTI) tractography in women with endometriosis and/or adenomyosis, and to analyze the correlations among DTI abnormalities, pain symptoms, and endometriotic lesions found at surgery. DesignA cross-sectional, observational study (Canadian Task Force classification II-2). SettingUniversity hospital. PatientsWomen (n = 76) with clinical suspicion of endometriosis. InterventionsBefore surgery, dysmenorrhea, deep dyspareunia, and noncyclic pelvic pain (NCPP) were assessed using a 10-point visual analog scale. MRI enabled a 3-dimensional reconstruction of S1, S2, and S3. Fractional anisotropy was calculated for each root. Laparoscopic treatment of endometriosis was performed in 56 patients. Measurements and Main ResultsOur findings revealed correlations among sacral root reconstruction by MRI-DTI, pain symptoms, and laparoscopic findings. DTI of sacral roots revealed a regular and homogeneous appearance in 17 patients (25.8%) and abnormalities in microstructure reconstruction, with fiber irregularities and disorganization and loss of the simple unidirectional course, in 44 patients (66.7%). At laparoscopy, ovarian endometriomas were found in 82.1% of the patients, and deeply infiltrating endometriosis (DIE) were found in 57.1%. Endometriosis was staged according to the revised American Society for Reproductive Medicine classification. Pathological DTI findings were significantly associated with the severity of dysmenorrhea and NCPP, pain duration, presence of tubo-ovarian and cul-de-sac adhesions, and DIE. ConclusionThe presence of pathological DTI findings of the sacral nerve roots correlates with the type of pain, adhesions, and DIE. At present, DTI can be useful for providing a better understanding of pain; however, DTI could become a useful tool in therapeutic planning for patients with endometriosis.

Rejection evaluation after renal transplantation using MR diffusion tensor imaging.

Background Renal allograft dysfunction monitoring is mainly performed using the serum creatinine (SC) level, Doppler ultrasound (US), or renal biopsy. Recently proposed diffusion-based magnetic resonance imaging (MRI) methods have been explored as new, non-invasive tools for assessing renal function after transplantation. Purpose To investigate the value of fractional anisotropy (FA) measurements in the evaluation of acute rejection cases after renal transplant. Material and Methods Doppler US and MRI diffusion tensor imaging (DTI) were performed in 21 patients with graft dysfunction requiring graft biopsy after renal transplantation and in 21 patients with normal graft function. The MR examinations were performed on a 1.5-T MRI using two b-values (0 and 800 s/mm2). FA values were measured from the cortex and medulla of the transplanted kidney at the upper, middle, and lower poles. Results Twenty-one transplant patients diagnosed with acute rejection (Group 1) were compared to the control group of 21 transplant patients with normal graft function (Group 2). The measured FA values of the medulla were 0.19 ± 0.02 and 0.22 ± 0.05 ( P = 0.017) for Groups 1 and 2, respectively. On the other hand, the measured FA values of the renal cortex were 0.18 ± 0.04 and 0.18 ± 0.04 ( P = 0.97) for Groups 1 and 2, respectively. Conclusion The good correlation between the renal medulla FA values and allograft function shows that MR DTI has potential for non-invasive functional assessment of transplanted kidneys. On the other hand, the renal cortex FA values had no correlation with the allograft function.

Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume.

To evaluate the added value of amide proton transfer (APT) imaging to the apparent diffusion coefficient (ADC) from diffusion tensor imaging (DTI) and the relative cerebral blood volume (rCBV) from perfusion magnetic resonance imaging (MRI) for discriminating between high- and low-grade gliomas. Forty-six consecutive adult patients with diffuse gliomas who underwent preoperative APT imaging, DTI and perfusion MRI were enrolled. APT signals were compared according to the World Health Organization grade. The diagnostic ability and added value of the APT signal to the ADC and rCBV for discriminating between low- and high-grade gliomas were evaluated using receiver operating characteristic (ROC) analyses and integrated discrimination improvement. The APT signal increased as the glioma grade increased. The discrimination abilities of the APT, ADC and rCBV values were not significantly different. Using both the APT signal and ADC significantly improved discrimination vs. the ADC alone (area under the ROC curve [AUC], 0.888 vs. 0.910; P = 0.007), whereas using both the APT signal and rCBV did not improve discrimination vs. the rCBV alone (AUC, 0.927 vs. 0.923; P = 0.222). APT imaging may be a useful imaging biomarker that adds value to the ADC for discriminating between low- and high-grade gliomas. • Higher APT values were correlated with higher glioma grades. • Adding the APT signal to the ADC improved glioma grading. • Adding the APT signal to rCBV did not improve glioma grading. • APT is a useful adjunct to the ADC for glioma grading.

Neuroregenerative potential of intravenous G-CSF and autologous peripheral blood stem cells in children with cerebral palsy: a randomized, double-blind, cross-over study

ObjectiveWe performed a randomized, double-blind, cross-over study to assess the neuroregenerative potential of intravenous granulocyte colony-stimulating factor (G-CSF) followed by infusion of mobilized peripheral blood mononuclear cells (mPBMCs) in children with cerebral palsy (CP).MethodsChildren with non-severe CP were enrolled in this study. G-CSF was administered for 5 days, then mPBMCs were collected by apheresis and cryopreserved. One month later (M1), recipients were randomized to receive either mPBMCs or a placebo infusion, and these treatment groups were switched at 7 months (M7) and observed for another 6 months (M13). We assessed the efficacy of treatment by evaluating neurodevelopmental tests, as well as by brain magnetic resonance imaging-diffusion tensor imaging (MRI-DTI) and 18F-fluorodeoxyglucose (FDG) brain positron emission tomography-computed tomography (PET-CT) scanning to evaluate the anatomical and functional changes in the brain.ResultsFifty-seven patients aged 4.3 ± 1.9 (range 2–10) years and weighing 16.6 ± 4.9 (range 11.6–56.0) kg were enrolled in this study. The administration of G-CSF as well as the collection and reinfusion of mPBMCs were safe and tolerable. The yield of mPBMCs was comparable to that reported in studies of pediatric donors without CP and patients with nonhematologic diseases. 42.6% of the patients responded to the treatment with higher neurodevelopmental scores than would normally be expected. In addition, larger changes in neurodevelopment test scores were observed in the 1 month after G-CSF administration (M0–M1) than during the 6 months after reinfusion with mPBMCs or placebo (M1–M7 or M7–M13). Patients who received G-CSF followed by mPBMC infusion at 7 months (T7 group) demonstrated significantly more neurodevelopmental improvement than patients who received G-CSF followed by mPBMC infusion at 1 month (T1 group). In contrast to the results of neurodevelopment tests, the results of MRI-DTI at the end of this study showed greater improvement in the T1 group. Although we observed metabolic changes to the cerebellum, thalamus and cerebral cortex in the 18F-FDG brain PET-CT scans, there were no significant differences in such changes between the mPBMC and placebo group or between the T1 and T7 group.ConclusionsNeurodevelopmental improvement was seen in response to intravenous G-CSF followed by mPBMC reinfusion, particularly to the G-CSF alone even without mPBMC reinfusion. Further studies using a larger number of mPBMCs for the infusion which could be collected by repeated cycles of apheresis or using repeated cycles of G-CSF alone, are needed to clarify the effect of mPBMC reinfusion or G-CSF alone (Trial registration: ClinicalTrials.gov, NCT02983708. Registered 5 December, 2016, retrospectively registered).

Interhemispheric functional connectivity in anorexia and bulimia nervosa.

The functional interplay between hemispheres is fundamental for behavioral, cognitive, and emotional control. Anorexia nervosa (AN) and bulimia nervosa (BN) have been largely studied with brain magnetic resonance imaging (MRI) in relation to the functional mechanisms of high-level processing, but not in terms of possible inter-hemispheric functional connectivity anomalies. Using resting-state functional MRI (fMRI), voxel-mirrored homotopic connectivity (VMHC) and regional inter-hemispheric spectral coherence (IHSC) were studied in 15 AN and 13 BN patients and 16 healthy controls (HC). Using T1-weighted and diffusion tensor imaging MRI scans, regional VMHC values were correlated with the left-right asymmetry of corresponding homotopic gray matter volumes and with the white matter callosal fractional anisotropy (FA). Compared to HC, AN patients exhibited reduced VMHC in cerebellum, insula, and precuneus, while BN patients showed reduced VMHC in dorso-lateral prefrontal and orbito-frontal cortices. The regional IHSC analysis highlighted that the inter-hemispheric functional connectivity was higher in the 'Slow-5' band in all regions except the insula. No group differences in left-right structural asymmetries and in VMHC vs. callosal FA correlations were significant in the comparisons between cohorts. These anomalies, not explained by structural changes, indicate that AN and BN, at least in their acute phase, are associated with a loss of inter-hemispheric connectivity in regions implicated in self-referential, cognitive control and reward processing. These findings may thus gather novel functional markers to explore aberrant features of these eating disorders.

Cellular and Morphological Alterations in the Vastus Lateralis Muscle as the Result of ACL Injury and Reconstruction.

Individuals who have had an anterior cruciate ligament (ACL) tear and reconstruction continue to experience substantial knee extensor strength loss despite months of physical therapy. Identification of the alterations in muscle morphology and cellular composition are needed to understand potential mechanisms of muscle strength loss, initially as the result of the injury and subsequently from surgery and rehabilitation. We performed diffusion tensor imaging-magnetic resonance imaging and analyzed muscle biopsies from the vastus lateralis of both the affected and unaffected limbs before surgery and again from the reconstructed limb following the completion of rehabilitation. Immunohistochemistry was done to determine fiber type and size, Pax-7-positive (satellite) cells, and extracellular matrix (via wheat germ agglutinin straining). Using the diffusion tensor imaging data, the fiber tract length, pennation angle, and muscle volume were determined, yielding the physiological cross-sectional area (PCSA). Paired t tests were used to compare the effects of the injury between injured and uninjured limbs and the effects of surgery and rehabilitation within the injured limb. We found significant reductions before surgery in type-IIA muscle cross-sectional area (CSA; p = 0.03), extracellular matrix (p < 0.01), satellite cells per fiber (p < 0.01), pennation angle (p = 0.03), muscle volume (p = 0.02), and PCSA (p = 0.03) in the injured limb compared with the uninjured limb. Following surgery, these alterations in the injured limb persisted and the frequency of the IIA fiber type decreased significantly (p < 0.01) and that of the IIA/X hybrid fiber type increased significantly (p < 0.01). Significant and prolonged differences in muscle quality and morphology occurred after ACL injury and persisted despite reconstruction and extensive physical therapy. These results suggest the need to develop more effective early interventions following an ACL tear to prevent deleterious alterations within the quadriceps.

ADHD and Cerebellar Vermis Tumor: DTI Analysis of an Incidental Finding

The increase in number of magnetic resonance imaging (MRI) scans for investigation of neurological diseases in childhood and adolescence leads to increase of incidental findings of central nervous system (CNS) tumors in these stages of life. Among MRI techniques, diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) have been increasingly used in brain studies. These images are based on random motion of water molecules in the body, which can change depending on constitution and geometry of biological tissues, as well as the existence of pathologies. This paper reports the use of DTI and DWI to evaluation of a CNS tumor incidentally detected in a patient diagnosed previously with Attention Deficit Hyperactivity Disorder (ADHD). He was diagnosed at age 9 and has been treated with medicines and psycho-pedagogical therapies. At age 15 a MRI detected a cerebellar vermis tumor with a volume of 2 cm 3 . Due to parental decision, the patient did not undergo any surgical intervention. During the follow-up period we did not observe significant changes in tumor size or diffusion directions in the tumor and surrounding brain tissues. The main brain tracts presented normal diffusion patterns, both in terms of size and geometry. The DTI analysis showed that lesion was quite homogeneous and isotropic, with no significant restriction of diffusion. There also were no significant diffusion pattern changes in other regions of the brain which possibly could be related to ADHD. So, given the characteristics of lesion and the patient's clinical symptoms, it cannot be directly related to ADHD.

Development of a Sensitive Outcome for Economical Drug Screening for Progressive Multiple Sclerosis Treatment.

Therapeutic advance in progressive multiple sclerosis (MS) has been very slow. Based on the transformative role magnetic resonance imaging (MRI) contrast-enhancing lesions had on drug development for relapsing-remitting MS, we consider the lack of sensitive outcomes to be the greatest barrier for developing new treatments for progressive MS. The purpose of this study was to compare 58 prospectively acquired candidate outcomes in the real-world situation of progressive MS trials to select and validate the best-performing outcome. The 1-year pre-treatment period of adaptively designed IPPoMS (ClinicalTrials.gov #NCT00950248) and RIVITaLISe (ClinicalTrials.gov #NCT01212094) Phase II trials served to determine the primary outcome for the subsequent blinded treatment phase by comparing 8 clinical, 1 electrophysiological, 1 optical coherence tomography, 7 MRI volumetric, 9 quantitative T1 MRI, and 32 diffusion tensor imaging MRI outcomes. Fifteen outcomes demonstrated significant progression over 1 year (Δ) in the predetermined analysis and seven out of these were validated in two independent cohorts. Validated MRI outcomes had limited correlations with clinical scales, relatively poor signal-to-noise ratios (SNR) and recorded overlapping values between healthy subjects and MS patients with moderate-severe disability. Clinical measures correlated better, even though each reflects a somewhat different disability domain. Therefore, using machine-learning techniques, we developed a combinatorial weight-adjusted disability score (CombiWISE) that integrates four clinical scales: expanded disability status scale (EDSS), Scripps neurological rating scale, 25 foot walk and 9 hole peg test. CombiWISE outperformed all clinical scales (Δ = 9.10%; p = 0.0003) and all MRI outcomes. CombiWISE recorded no overlapping values between healthy subjects and disabled MS patients, had high SNR, and predicted changes in EDSS in a longitudinal assessment of 98 progressive MS patients and in a cross-sectional cohort of 303 untreated subjects. One point change in EDSS corresponds on average to 7.50 point change in CombiWISE with a standard error of 0.10. The novel validated clinical outcome, CombiWISE, outperforms the current broadly utilized MRI brain atrophy outcome and more than doubles sensitivity in detecting clinical deterioration in progressive MS in comparison to the scale traditionally used for regulatory approval, EDSS.

Pre-operative declining proportion of fractional anisotropy of trigeminal nerve is correlated with the outcome of micro-vascular decompression surgery.

BackgroundType 2 trigeminal neuralgia (TN) is an intractable neuropathic pain syndrome compared with type 1 TN because of the difficulty of diagnosis as well as the unsatisfactory prognosis. Neurovascular compression (NVC) is considered the major pathology of TN. Routine magnetic resonance imaging (MRI) sequences are inadequate for revealing the effect of NVC which is related to the surgical decision and outcome. The decreasing of fractional anisotropy (FA), one of the MRI diffusion tensor imaging (DTI) metrics, is correlated with the demyelination of trigeminal nerve (TGN) that reveal the severity of NVC.MethodsA retrospective review of patients treated with micro-vascular decompression (MVD) surgery was undertaken. All the patients were diagnosed as type 2 TN. FA of TGN of both sides were measured. The FA declining proportion = ((the mean FA value of healthy lateral)-(the mean FA value of the symptomatic lateral))/(the mean FA value of healthy lateral). Declining proportion of FA value, discovery of surgery and outcome of MVD were recorded and analyzed. Logistic regression analysis and linear regression analysis were employed to analyze the risk factors of declining proportion of FA value and MVD outcome.ResultsNineteen patients were assessed in our study. The average declining proportion of FA value for all patients was 0.25 ± 0.12. The average declining proportion of FA value of “success” and “failure” group was 0.32 ± 0.09 to 0.14 ± 0.10 (P = 0.002 < 0.05). The declining proportion of FA value of artery (including the artery plus vein situation) was 0.34 ± 0.06 in contrast to 0.15 ± 0.08 of vein (P = 0.000 < 0.05). MVD outcome was correlated with declining proportion of FA value (AUC = 0.900). Furthermore, declining proportion of FA value was higher in arterial compression situation.ConclusionFA value quantitatively showed the alteration of TGN caused by NVC. It provided direct evidence about the effect of NVC which facilitated the diagnosis and surgical decision of type 2 TN. Besides, significant reduction of FA value may predict an optimistic outcome of MVD.