Focused Ultrasound Central Lateral Thalamotomy for the Treatment of Refractory Neuropathic Pain: Phase I Trial.

BACKGROUND AND OBJECTIVES: Magnetic resonance-guided focused ultrasound (MRgFUS) central lateral thalamotomy (CLT) has not yet been validated for treating refractory neuropathic pain (NP). Our aim was to assess the safety and potential efficacy of MRgFUS CLT for refractory NP. METHODS: In this prospective, nonrandomized, single-arm, investigator-initiated phase I trial, patients with NP for more than 6 months related to phantom limb pain, spinal cord injury, or radiculopathy/radicular injury and who had undergone at least one previous failed intervention were eligible. The main outcomes were safety profile and pain as assessed using the brief pain inventory, the pain disability index, and the numeric rating scale. Medication use and the functional connectivity of the default mode network (DMN) were also assessed. RESULTS: Ten patients were enrolled, with nine achieving successful ablation. There were no serious adverse events and 12 mild/moderate severity events. The mean age was 50.9 years (SD: 12.7), and the mean symptom duration was 12.3 years (SD: 9.7). Among eight patients with a 1-year follow-up, the brief pain inventory decreased from 7.6 (SD: 1.1) to 3.8 (SD: 2.8), with a mean percent decrease of 46.3 (SD: 40.6) (paired t -test, P = .017). The mean pain disability index decreased from 43.0 (SD: 7.5) to 25.8 (SD: 16.8), with a mean percent decrease of 39.3 (SD: 41.6) ( P = .034). Numeric rating scale scores decreased from a mean of 7.2 (SD: 1.8) to 4.0 (SD: 2.8), with a mean percent decrease of 42.8 (SD: 37.8) ( P = .024). Patients with predominantly intermittent pain or with allodynia responded better than patients with continuous pain or without allodynia, respectively. Some patients decreased medication use. Resting-state functional connectivity changes were noted, from disruption of the DMN at baseline to reactivation of connectivity between DMN nodes at 3 months. CONCLUSION: MRgFUS CLT is feasible and safe for refractory NP and has potential utility in reducing symptoms as measured by validated pain scales.

The University of Pennsylvania glioblastoma (UPenn-GBM) cohort: advanced MRI, clinical, genomics, & radiomics.

Glioblastoma is the most common aggressive adult brain tumor. Numerous studies have reported results from either private institutional data or publicly available datasets. However, current public datasets are limited in terms of: a) number of subjects, b) lack of consistent acquisition protocol, c) data quality, or d) accompanying clinical, demographic, and molecular information. Toward alleviating these limitations, we contribute the "University of Pennsylvania Glioblastoma Imaging, Genomics, and Radiomics" (UPenn-GBM) dataset, which describes the currently largest publicly available comprehensive collection of 630 patients diagnosed with de novo glioblastoma. The UPenn-GBM dataset includes (a) advanced multi-parametric magnetic resonance imaging scans acquired during routine clinical practice, at the University of Pennsylvania Health System, (b) accompanying clinical, demographic, and molecular information, (d) perfusion and diffusion derivative volumes, (e) computationally-derived and manually-revised expert annotations of tumor sub-regions, as well as (f) quantitative imaging (also known as radiomic) features corresponding to each of these regions. This collection describes our contribution towards repeatable, reproducible, and comparative quantitative studies leading to new predictive, prognostic, and diagnostic assessments.

Improving Sensitivity of Arterial Spin Labeling Perfusion MRI in Alzheimer's Disease Using Transfer Learning of Deep Learning-Based ASL Denoising.

BACKGROUND: Arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) denoising through deep learning (DL) often faces insufficient training data from patients. One solution is to train DL models using healthy subjects' data which are more widely available and transfer them to patients' data. PURPOSE: To evaluate the transferability of a DL-based ASL MRI denoising method (DLASL). STUDY TYPE: Retrospective. SUBJECTS: Four hundred and twenty-eight subjects (189 females) from three cohorts. FIELD STRENGTH/SEQUENCE: 3 T two-dimensional (2D) echo-planar imaging (EPI)-based pseudo-continuous ASL (PCASL) and 2D EPI-based pulsed ASL (PASL) sequences. ASSESSMENT: DLASL was trained using young healthy adults' PCASL data (Dataset 1: 250/30 subjects as training/validation set) and was directly transferred (DTF) to PCASL data from Dataset 2 (45 subjects test set) of normal controls (NC) and Alzheimer's disease (AD) groups. DLASL was fine-tuned (DLASLFT) and tested on PASL data from Dataset 3 (103 subjects test set) of NC and AD. An existing non-DL method (NonDL) was used for comparison. Cerebral blood flow (CBF) images from ASL MRI were compared between NC and AD to assess characteristic hypoperfusion (lower CBF) patterns in AD. CBF image quality and CBF map sensitivity for detecting hypoperfusion using peak t-value and suprathreshold cluster size are outcome measures. STATISTICAL TESTS: Paired t-test, two-sample t-test, one-way analysis of variance, and Tukey honestly significant difference, and linear mixed-effects models were used. P < 0.05 was considered statistically significant. RESULTS: Mean contrast-to-noise ratio (CNR) of Dataset 2 showed that DTF outperformed NonDL (AD: 3.38 vs. 2.64, NC: 3.80 vs. 3.36). On Dataset 3, DLASLFT outperformed NonDL measured by mean CNR (AD: 2.45 vs. 1.87, NC: 2.54 vs. 2.17) and mean radiologic score (2.86 vs. 2.44). Image quality improvement was significant on both test sets. DTF and DLASLFT improved sensitivity for detecting AD-related hypoperfusion patterns compared with NonDL. DATA CONCLUSION: We demonstrated the DLASL's transferability across different ASL sequences and different populations. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

MRI Guided Focused Ultrasound-Mediated Delivery of Therapeutic Cells to the Brain: A Review of the State-of-the-Art Methodology and Future Applications.

Stem cell and immune cell therapies are being investigated as a potential therapeutic modality for CNS disorders, performing functions such as targeted drug or growth factor delivery, tumor cell destruction, or inflammatory regulation. Despite promising preclinical studies, delivery routes for maximizing cell engraftment, such as stereotactic or intrathecal injection, are invasive and carry risks of hemorrhage and infection. Recent developments in MRI-guided focused ultrasound (MRgFUS) technology have significant implications for treating focal CNS pathologies including neurodegenerative, vascular and malignant processes. MRgFUS is currently employed in the clinic for treating essential tremor and Parkinson's Disease by producing precise, incisionless, transcranial lesions. This non-invasive technology can also be modified for non-destructive applications to safely and transiently open the blood-brain barrier (BBB) to deliver a range of therapeutics, including cells. This review is meant to familiarize the neuro-interventionalist with this topic and discusses the use of MRgFUS for facilitating cellular delivery to the brain. A detailed and comprehensive description is provided on routes of cell administration, imaging strategies for targeting and tracking cellular delivery and engraftment, biophysical mechanisms of BBB enhanced permeability, supportive proof-of-concept studies, and potential for clinical translation.

Enhancing Metabolic Imaging of Energy Metabolism in Traumatic Brain Injury Using Hyperpolarized [1-13C]Pyruvate and Dichloroacetate.

Hyperpolarized magnetic resonance spectroscopic imaging (MRSI) of [1-13C]pyruvate metabolism has previously been used to assess the effects of traumatic brain injury (TBI) in rats. Here, we show that MRSI can be used in conjunction with dichloroacetate to measure the phosphorylation state of pyruvate dehydrogenase (PDH) following mild-to-moderate TBI, and that measurements can be repeated in a longitudinal study to monitor the course of injury progression and recovery. We found that the level of 13C-bicarbonate and the bicarbonate-to-lactate ratio decreased on the injured side of the brain four hours after injury and continued to decrease through day 7. Levels recovered to normal by day 28. Measurements following dichloroacetate administration showed that PDH was inhibited equally by PDH kinase (PDK) on both sides of the brain. Therefore, the decrease in aerobic metabolism is not due to inhibition by PDK.

Technical Comparison of Treatment Efficiency of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy and Pallidotomy in Skull Density Ratio-Matched Patient Cohorts.

OBJECTIVE: MR-guided focused ultrasound (MRgFUS) is increasingly being used to treat patients with essential tremor (ET) and Parkinson's disease (PD) with thalamotomy and pallidotomy, respectively. Pallidotomy is performed off-center within the cranium compared to thalamotomy and may present challenges to therapeutic lesioning due to this location. However, the impact of target location on treatment efficiency and ability to create therapeutic lesions has not been studied. This study aimed to compare the physical efficiency of MRgFUS thalamotomy and pallidotomy. METHODS: Treatment characteristics were compared between patients treated with thalamotomy (n = 20) or pallidotomy (n = 20), matched by skull density ratios (SDR). Aspects of treatment efficiency were compared between these groups. Demographic and comparative statistics were conducted to assess these differences. Acoustic field simulations were performed to compare and validate the simulated temperature profile for VIM and GPi ablation. RESULTS: Lower SDR values were associated with greater energy requirement for thalamotomy (R2 = 0.197, p = 0.049) and pallidotomy (R2 = 0.342, p = 0.007). The impact of low SDR on efficiency reduction was greater for pallidotomy, approaching significance (p = 0.061). A nearly two-fold increase in energy was needed to reach 50°C in pallidotomy (10.9kJ) than in thalamotomy (5.7kJ), (p = 0.002). Despite lower energy requirement, the maximum average temperature reached was higher in thalamotomy (56.7°C) than in pallidotomy (55.0°C), (p = 0.017). Mean incident angle of acoustic beams was lesser in thalamotomy (12.7°) than in pallidotomy (18.6°), (p < 0.001). For all patients, a lesser mean incident angle correlated with a higher maximum average temperature reached (R2 = 0.124, p = 0.026), and less energy needed to reach 50°C (R2=0.134, p = 0.020). Greater skull thickness was associated with a higher maximum energy for a single sonication for thalamotomy (R2 = 0.206, p = 0.045) and pallidotomy (R2 = 0.403, p = 0.003). An acoustic and temperature field simulation validated similar findings for thalamotomy and pallidotomy in a single patient. CONCLUSION: The centrally located VIM offers a more efficient location for therapeutic lesioning compared to GPi pallidotomy in SDR matched cohort of patients. The impact on therapeutic lesioning with lower SDR may be greater for pallidotomy patients. As newer off-center targets are investigated, these findings can inform patient selection and treatment requirements for lesion production.

Predicting final lesion characteristics during MR-guided focused ultrasound pallidotomy for treatment of Parkinson's disease.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) ablation of the globus pallidus interna (GPi) is being investigated for the treatment of advanced Parkinson's disease symptoms. However, GPi lesioning presents unique challenges due to the off-midline location of the target. Furthermore, it remains uncertain whether intraprocedural MR thermometry data can predict final lesion characteristics. METHODS: The authors first performed temperature simulations of GPi pallidotomy and compared the results with those of actual cases and the results of ventral intermediate nucleus (VIM) thalamotomy performed for essential tremor treatment. Next, thermometry data from 13 MRgFUS pallidotomy procedures performed at their institution were analyzed using 46°C, 48°C, 50°C, and 52°C temperature thresholds. The resulting thermal models were compared with resulting GPi lesions noted on postprocedure days 1 and 30. Finally, the treatment efficiency (energy per temperature rise) of pallidotomy was evaluated. RESULTS: The authors' modeled acoustic intensity maps correctly demonstrate the elongated, ellipsoid lesions noted during GPi pallidotomy. In treated patients, the 48°C temperature threshold maps most accurately predicted postprocedure day 1 lesion size, while no correlation was found for day 30 lesions. The average energy/temperature rise of pallidotomy was higher (612 J/°C) than what had been noted for VIM thalamotomy and varied with the patients' skull density ratios (SDRs). CONCLUSIONS: The authors' acoustic simulations accurately depicted the characteristics of thermal lesions encountered following MRgFUS pallidotomy. MR thermometry data can predict postprocedure day 1 GPi lesion characteristics using a 48°C threshold model. Finally, the lower treatment efficiency of pallidotomy may make GPi lesioning challenging in patients with a low SDR.

Targeting of the dentato-rubro-thalamic tract for MR-guided focused ultrasound treatment of essential tremor.

BACKGROUND: Magnetic resonance-guided focused ultrasound ablation of the thalamic ventral intermediate nucleus is a safe and effective treatment for medically refractory essential tremor. However, indirect targeting of the ventral intermediate nucleus using stereotactic coordinates from normal neuroanatomy can be inefficient. We therefore evaluated the feasibility of supplementing this method with direct targeting of the dentato-rubro-thalamic tract. METHODS: We retrospectively identified four patients undergoing magnetic resonance-guided focused ultrasound ablation for essential tremor in which preoperative diffusion tractography imaging of the dentato-rubro-thalamic tract was fused with T2 weighted-imaging and utilized for intra-procedural targeting. The size and location of the dentato-rubro-thalamic tract and 24-hour lesion, as well as the center of the stereotactic coordinates, was evaluated. Finally, the amount of overlap between the dentato-rubro-thalamic tract and the lesion was calculated. RESULTS: The 24-hour lesion size was homogeneous in the cohort (mean 31.3 mm2, range 30-32 mm2), while there was substantial variation in the dentato-rubro-thalamic tract area (mean 14.3 mm2, range 3-24 mm2). The center of the stereotactic coordinates and dentato-rubro-thalamic tract diverged by more than 1 mm in mediolateral and anterposterior directions in all patients, while the dentato-rubro-thalamic tract and lesion centers were in close proximity (mean mediolateral separation 1 mm, range 0.1-2.2 mm; mean anteroposterior separation 0.75 mm, range 0.4-1.2 mm). There was greater than 50% coverage of the dentato-rubro-thalamic tract by the lesion in all patients (mean 82.9%, range 66.7-100%). All patients experienced durable tremor relief. CONCLUSION: Direct targeting of the dentato-rubro-thalamic tract using diffusion tractography imaging fused to T2 weighted-imaging may be a useful strategy for focused ultrasound treatment of essential tremor. Further investigation of the technique is warranted.

Lack of choline elevation on proton magnetic resonance spectroscopy in grade I-III gliomas.

Elevated levels of choline are generally emphasized as marker of increased cellularity and cell membrane turnover in gliomas. In this study, we investigated the incidence rate of lack of choline/creatine and choline/water elevation in a population of grade I-III gliomas. A cohort of 41 patients with histopathologically confirmed gliomas underwent multi-voxel proton magnetic resonance spectroscopy on a 3 T magnetic resonance system prior to treatment. Peak areas for choline and myoinositol were measured from all voxels that exhibited hyperintensity on fluid-attenuated inversion recovery images and were normalized to creatine and unsuppressed water from each voxel. The average metabolite/creatine and metabolite/water ratios from these voxels were then computed. Similarly, average metabolite ratios were computed from normal brain parenchyma. Gliomas were considered for lack of choline elevation when choline/creatine and choline/water ratios from neoplastic regions were less than those from normal brain parenchyma regions. Six of 41 (14.6%) grade I-III gliomas showed lack of elevation for choline/creatine and choline/water ratios compared to normal brain parenchyma. Four of these six gliomas also demonstrated elevated levels of myoinositol/creatine ratio. All other gliomas (n = 35) had elevated choline levels from neoplastic regions relative to normal parenchyma. The sensitivity of choline/creatine or choline/water in determining a grade I-III glioma was 85.4%. These findings suggest that a lack of choline/creatine or choline/water elevation may be seen in some gliomas and low choline levels should not prevent us from considering the possibility of a grade I-III glioma.

Feasibility of ultrashort echo time images using full-wave acoustic and thermal modeling for transcranial MRI-guided focused ultrasound (tcMRgFUS) planning.

Transcranial MRI-guided focused ultrasound (tcMRgFUS) is increasingly used to non-invasively treat a wide variety of neurological disorders including essential tremors, Parkinson's disease, and neuropathic pain. Although this treatment is an MRI-guided procedure, the current pre-treatment screening and planning involve a CT of the head to obtain 3D skull images. These images are necessary for estimating the proportion of absorbed energy and the acoustic phase shift associated with the skull and determining the transmit energy of ultrasonic waves to create thermal lesions at a desired focal spot. Ultrashort echo time (UTE) MR sequences can capture signals from tissues such as bone which have a very short transverse relaxation time. In this manuscript, we assess the use of a UTE based sequence to image the calvarium and test the feasibility of obviating the need for CT based imaging during an MR-guided focused ultrasound therapy. We demonstrate that the segmentation of bone using UTE images leads to similar skull density ratio values as determined from CT with high correlation (r = 0.88; p  < 0.0001). Furthermore, through treatment specific modeling we demonstrate that the thermal profiles and focal locations are in concordance with the actual treatment plan when using the UTE based skull intensity information suggesting the possibility of replacing the CT scans with UTE based skull imaging in all tcMRgFUS procedures, potentially eliminating unnecessary radiation exposure. Overall, the results indicate that UTE MR imaging may serve as an effective and accurate alternative to CT imaging for both screening and pre-treatment planning on patients undergoing the tcMRgFUS procedure.

Metabolic imaging of energy metabolism in traumatic brain injury using hyperpolarized [1-13C]pyruvate.

Traumatic brain injury (TBI) is known to cause perturbations in the energy metabolism of the brain, but current tests of metabolic activity are only indirect markers of energy use or are highly invasive. Here we show that hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) can be used as a direct, non-invasive method for studying the effects of TBI on energy metabolism. Measurements were performed on rats with moderate TBI induced by controlled cortical impact on one cerebral hemisphere. Following injection of hyperpolarized [1-13C]pyruvate, the resulting 13C-bicarbonate signal was found to be 24 ± 6% lower in the injured hemisphere compared with the non-injured hemisphere, while the hyperpolarized bicarbonate-to-lactate ratio was 33 ± 8% lower in the injured hemisphere. In a control group, no significant difference in signal was found between sides of the brain. The results suggest an impairment in mitochondrial pyruvate metabolism, resulting in a decrease in aerobic respiration at the location of injury following TBI.

Brain morphometric analysis predicts decline of intelligence quotient in children with sickle cell disease: A preliminary study.

PURPOSE: For children with sickle cell disease (SCD) and at low risk category of stroke, we aim to build a predictive model to differentiate those with decline of intelligence-quotient (IQ) from counterparts without decline, based on structural magnetic-resonance (MR) imaging volumetric analysis. MATERIALS AND METHODS: This preliminary prospective cohort study included 25 children with SCD, homozygous for hemoglobin S, with no history of stroke and transcranial Doppler mean velocities below 170cm/s at baseline. We administered the Kaufman Brief Intelligence Test (K-BIT) to each child at yearly intervals for 2-4 years. Each child underwent MR examination within 30 days of the baseline K-BIT evaluation date. We calculated K-BIT change rates, and used rate of change in K-BIT to classify children into two groups: a decline group and a non-decline group. We then generated predictive models to predict K-BIT decline/non-decline based on regional gray-matter (GM) volumes computed from structural MR images. RESULTS: We identified six structures (the left median cingulate gyrus, the right middle occipital gyrus, the left inferior occipital gyrus, the right fusiform gyrus, the right middle temporal gyrus, the right inferior temporal gyrus) that, when assessed for volume at baseline, are jointly predictive of whether a child would suffer subsequent K-BIT decline. Based on these six regional GM volumes and the baseline K-BIT, we built a prognostic model using the K* algorithm. The accuracy, sensitivity and specificity were 0.84, 0.78 and 0.86, respectively. CONCLUSIONS: GM volumetric analysis predicts subsequent IQ decline for children with SCD.

Assignment Confidence in Localization of the Hand Motor Cortex: Comparison of Structural Imaging With Functional MRI.

OBJECTIVE: The purpose of this study was to assign confidence levels to structural MRI and functional MRI (fMRI) for localization of the primary motor cortex. MATERIALS AND METHODS: Ninety-one fMRI studies with at least one motor task (178 hemispheres) were identified. Three anatomic assessments were used to localize the primary motor cortex: relation between the superior frontal sulcus and precentral sulcus; cortical thickness; and configuration of the precentral knob. In 105 hemispheres, interreader agreement was assessed for two investigators with different experience levels. Confidence ratings from 0 to 5 (0, no confidence; 5, 100% confidence) were assigned for fMRI and each anatomic localization method. RESULTS: Cortical thickness had the highest confidence rating (mean, 4.90 ± 0.47 [SD]) with only one failure. The relation between the superior frontal sulcus and precentral sulcus had the lowest confidence rating (4.33 ± 0.91) with three failures. The greatest statistical significance was observed for the cortical thickness and superior frontal sulcus-precentral sulcus methods (post hoc Bonferroni test, p < 0.001). Confidence rating scores were significantly higher for the cortical thickness sign than for fMRI results (4.72 ± 0.54) for a single motor task (post hoc Bonferroni test, p = 0.006); however, the mean confidence rating for fMRI improved to 4.87 ± 0.36 when additional motor tasks were performed. Interreader differences were least for the cortical thickness sign (paired t test, t = 4.25, p < 0.001). CONCLUSION: Cortical thickness is a better anatomic landmark than fMRI localization for assigning confidence regarding localization of the primary motor cortex; however, localization of motor function is more specific when combined with fMRI findings. Multiple techniques can be used to increase confidence in identifying the hand motor cortex.

Gender-based analysis of cortical thickness and structural connectivity in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurological disorder and appears to have gender-specific symptoms. Studies have observed a higher frequency for development of PD in male than in female. In the current study, we evaluated the gender-based changes in cortical thickness and structural connectivity in PD patients. With informed consent, 64 PD (43 males and 21 females) patients, and 46 (12 males and 34 females) age-matched controls underwent clinical assessment including Mini-Mental State Examination (MMSE) and magnetic resonance imaging on a 1.5 Tesla clinical MR scanner. Whole brain high-resolution T1-weighted images were acquired from all subjects and used to measure cortical thickness and structural network connectivity. No significant difference in MMSE score was observed between male and female both in control and PD subjects. Male PD patients showed significantly reduced cortical thickness in multiple brain regions including frontal, parietal, temporal, and occipital lobes as compared with those in female PD patients. The graph theory-based network analysis depicted lower connection strengths, lower clustering coefficients, and altered network hubs in PD male than in PD female. Male-specific cortical thickness changes and altered connectivity in PD patients may derive from behavioral, physiological, environmental, and genetical differences between male and female, and may have significant implications in diagnosing and treating PD among genders.

Metabolic, endocrine, and other genetic disorders.

Metabolic, endocrine, and genetic diseases of the brain include a very large array of disorders caused by a wide range of underlying abnormalities and involving a variety of brain structures. Often these disorders manifest as recognizable, though sometimes overlapping, patterns on neuroimaging studies that may enable a diagnosis based on imaging or may alternatively provide enough clues to direct further diagnostic evaluation. The diagnostic workup can include various biochemical laboratory or genetic studies. In this chapter, after a brief review of normal white-matter development, we will describe a variety of leukodystrophies resulting from metabolic disorders involving the brain, including mitochondrial and respiratory chain diseases. We will then describe various acidurias, urea cycle disorders, disorders related to copper and iron metabolism, and disorders of ganglioside and mucopolysaccharide metabolism. Lastly, various other hypomyelinating and dysmyelinating leukodystrophies, including vanishing white-matter disease, megalencephalic leukoencephalopathy with subcortical cysts, and oculocerebrorenal syndrome will be presented. In the following section on endocrine disorders, we will examine various disorders of the hypothalamic-pituitary axis, including developmental, inflammatory, and neoplastic diseases. Neonatal hypoglycemia will also be briefly reviewed. In the final section, we will review a few of the common genetic phakomatoses. Throughout the text, both imaging and brief clinical features of the various disorders will be discussed.

Limbic pathway lesions in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a well-known demyelinating disease to cause cognitive dysfunction. The limbic system, relevant to memory, can be easily overlooked in conventional magnetic resonance imaging (MRI). PURPOSE: To investigate the distribution and frequency of demyelinating lesions affecting white matter connections of the limbic system based on localization with diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) color maps compared to three-dimensional T2-weighted (T2W) and FLAIR volumes in MS patients. MATERIAL AND METHODS: One hundred and fifty patients with a known diagnosis of MS were identified for this Health Insurance Portability and Accountability (HIPAA)-compliant retrospective cross-sectional study. DTI-derived FA color maps, co-registered to T2W and FLAIR images, were analyzed for lesions affecting the three white matter tracts of the limbic system including cingulum, fornix, and mammilothalamic tracts by two investigators. The approximate location of the lesions on FLAIR was always confirmed on the co-registered DTI-derived FA color maps. RESULTS: Of the 150 patients analyzed, 14.6% had cingulum lesions, 2.6% had fornix lesions, and 2.6% had mammilothalamic tract lesions; 21.3% of patients had at least one of the three tracts affected. CONCLUSION: A relatively high frequency of lesions involving the limbic tracts may explain memory deficits and emotional dysfunction commonly experienced by patients with MS. The combined information from T2W, FLAIR, and DTI-derived FA color map allowed for more accurate localization of lesions affecting the major white matter tracts of the limbic system.

T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease.

In the current study, we have evaluated the performance of magnetic resonance (MR) T1rho (T1ρ) imaging and CSF biomarkers (T-tau, P-tau and Aß-42) in characterization of Alzheimer's disease (AD) patients from mild cognitive impairment (MCI) and control subjects. With informed consent, AD (n = 27), MCI (n = 17) and control (n = 17) subjects underwent a standardized clinical assessment and brain MRI on a 1.5-T clinical-scanner. T1ρ images were obtained at four different spin-lock pulse duration (10, 20, 30 and 40 ms). T1ρ maps were generated by pixel-wise fitting of signal intensity as a function of the spin-lock pulse duration. T1ρ values from gray matter (GM) and white matter (WM) of medial temporal lobe were calculated. The binary logistic regression using T1ρ and CSF biomarkers as variables was performed to classify each group. T1ρ was able to predict 77.3% controls and 40.0% MCI while CSF biomarkers predicted 81.8% controls and 46.7% MCI. T1ρ and CSF biomarkers in combination predicted 86.4% controls and 66.7% MCI. When comparing controls with AD, T1ρ predicted 68.2% controls and 73.9% AD, while CSF biomarkers predicted 77.3% controls and 78.3% for AD. Combination of T1ρ and CSF biomarkers improved the prediction rate to 81.8% for controls and 82.6% for AD. Similarly, on comparing MCI with AD, T1ρ predicted 35.3% MCI and 81.9% AD, whereas CSF biomarkers predicted 53.3% MCI and 83.0% AD. Collectively CSF biomarkers and T1ρ were able to predict 59.3% MCI and 84.6% AD. On receiver operating characteristic analysis T1ρ showed higher sensitivity while CSF biomarkers showed greater specificity in delineating MCI and AD from controls. No significant correlation between T1ρ and CSF biomarkers, between T1ρ and age, and between CSF biomarkers and age was observed. The combined use of T1ρ and CSF biomarkers have promise to improve the early and specific diagnosis of AD. Furthermore, disease progression form MCI to AD might be easily tracked using these two parameters in combination.

Association of dynamic susceptibility contrast enhanced MR Perfusion parameters with prognosis in elderly patients with glioblastomas.

OBJECTIVES: We aimed to evaluate the prognostic value of dynamic susceptibility contrast (DSC) MR perfusion in elderly patients with glioblastomas (GBM). METHODS: Thirty five patients aged ≥65 and 35 aged <65 years old, (referred to as elderly and younger, respectively) were included in this retrospective study. The median relative cerebral volume (rCBV) from the enhancing region (rCBVER-Med) and immediate peritumoral region (rCBVIPR-Med) and maximum rCBV from the enhancing region of the tumor (rCBVER-Max) were compared and correlated with survival data. Analysis was repeated after rCBVs were dichotomized into high and low values and after excluding elderly patients who did not receive postoperative chemoradiation (34.3%). Kaplan-Meyer survival curves and parametric and semi-parametric regression tests were used for analysis. RESULTS: All rCBV parameters were higher in elderly compared to younger patients (p < 0.05). After adjustment for age, none were independently associated with shorter survival (p > 0.05). After rCBV dichotomization into high and low values, high rCBV in elderly was independently associated with shorter survival compared to low rCBV in elderly, or any rCBV in younger patients (p < 0.05). CONCLUSION: rCBV can be an imaging biomarker to identify a subgroup of GBM patients in the elderly with worse prognosis compared to others. KEY POINTS: • GBM perfusion parameters are higher in elderly compared to younger patients. • rCBV can identify a subgroup of elderly patients with worse prognosis. • rCBV can be an imaging biomarker for prognostication in GBM. • The identified elderly patients may benefit from anti-angiogenic treatment.