Identification of a single-dose, low flip angle based CBV threshold for fractional tumor burden (FTB) mapping in recurrent glioblastoma.

BACKGROUND AND PURPOSE: DSC-MRI can be used to generate fractional tumor burden (FTB) maps, via application of relative CBV thresholds, to spatially differentiate glioblastoma recurrence from post treatment radiation effects (PTRE). Image-localized histopathology was previously used to validate FTB maps derived from a reference DSC-MRI protocol using preload, a moderate flip angle (MFA, 60°) and post-processing leakage correction. Recently, a DSC-MRI protocol with a low flip angle (LFA, 30°) with no preload was shown to provide leakage-corrected RCBV equivalent to the reference protocol. This study aims to identify the RCBV thresholds for the LFA protocol that generate the most accurate FTB maps, concordant with those obtained from the reference MFA protocol. MATERIALS AND METHODS: Fifty-two patients with grade IV GBM who had prior surgical resection and received chemotherapy and radiotherapy were included in the study. Two sets of DSC-MRI data were collected sequentially first using LFA protocol with no preload, which served as the preload for the subsequent MFA protocol. Standardized relative CBV maps (sRCBV) were obtained for each patient and co-registered with the anatomical post-contrast T1-weighted images. The reference MFA-based FTB maps were computed using previously published sRCBV thresholds (1.0 and 1.56). An ROC analysis was conducted to identify the optimal, voxelwise LFA sRCBV thresholds, and the sensitivity, specificity, and accuracy of the LFA-based FTB maps were computed with respect to the MFA-based reference. RESULTS: The mean sRCBV values of tumors across patients exhibited strong agreement (CCC = 0.99) between the two protocols. Using the ROC analysis, the optimal lower LFA threshold that accurately distinguishes PTRE from tumor recurrence was found to be 1.0 (sensitivity: 87.77%; specificity: 90.22%), equivalent to the ground truth. To identify aggressive tumor regions, the ROC analysis identified an upper LFA threshold of 1.37 (sensitivity: 90.87%; specificity: 91.10%) for the reference MFA threshold of 1.56. CONCLUSION: For LFA-based FTB maps, a sRCBV threshold of 1.0 and 1.37 can differentiate PTRE from recurrent tumor. FTB maps aids in surgical planning, guiding pathological diagnosis and treatment strategies in the recurrent setting. This study further confirms the reliability of single-dose LFA-based DSC-MRI. ABBREVIATIONS: LFA = low flip angle; MFA = moderate flip angle; sRCBV = standardized relative cerebral blood volume; FTB = fractional tumor burden; PTRE = post treatment radiation effects; ROC = receiver operating characteristics; CCC = concordance correlation coefficient.

A 3D dual-echo spiral sequence for simultaneous dynamic susceptibility contrast and dynamic contrast-enhanced MRI with single bolus injection.

PURPOSE: Perfusion MRI reveals important tumor physiological and pathophysiologic information, making it a critical component in managing brain tumor patients. This study aimed to develop a dual-echo 3D spiral technique with a single-bolus scheme to simultaneously acquire both dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) data and overcome the limitations of current EPI-based techniques. METHODS: A 3D spiral-based technique with dual-echo acquisition was implemented and optimized on a 3T MRI scanner with a spiral staircase trajectory and through-plane SENSE acceleration for improved speed and image quality, in-plane variable-density undersampling combined with a sliding-window acquisition and reconstruction approach for increased speed, and an advanced iterative deblurring algorithm. Four volunteers were scanned and compared with the standard of care (SOC) single-echo EPI and a dual-echo EPI technique. Two patients were scanned with the spiral technique during a preload bolus and compared with the SOC single-echo EPI collected during the second bolus injection. RESULTS: Volunteer data demonstrated that the spiral technique achieved high image quality, reduced geometric artifacts, and high temporal SNR compared with both single-echo and dual-echo EPI. Patient perfusion data showed that the spiral acquisition achieved accurate DSC quantification comparable to SOC single-echo dual-dose EPI, with the additional DCE information. CONCLUSION: A 3D dual-echo spiral technique was developed to simultaneously acquire both DSC and DCE data in a single-bolus injection with reduced contrast use. Preliminary volunteer and patient data demonstrated increased temporal SNR, reduced geometric artifacts, and accurate perfusion quantification, suggesting a competitive alternative to SOC-EPI techniques for brain perfusion MRI.

Rapid T 2 ∗ -weighted MRI using multishot EPI with retrospective motion and phase correction in the emergency department.

PURPOSE: Brain MRI is increasingly used in the emergency department (ED), where T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted MRI is an essential tool for detecting hemorrhage and stroke. The goal of this study was to develop a rapid T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted MRI technique capable of correcting motion-induced artifacts, thereby simultaneously improving scan time and motion robustness for ED applications. METHODS: A 2D gradient-echo (GRE)-based multishot EPI (msEPI) technique was implemented using a navigator echo for estimating motion-induced errors. Bulk rigid head motion and phase errors were retrospectively corrected using an iterative conjugate gradient approach in the reconstruction pipeline. Three volunteers and select patients were imaged at 3 T and/or 1.5 T with an approximately 1-min full-brain protocol using the proposed msEPI technique and compared to an approximately 3-min standard-of-care GRE protocol to examine its performance. RESULTS: Data from volunteers demonstrated that in-plane motion artifacts could be effectively corrected with the proposed msEPI technique, and through-plane motion artifacts could be mitigated. Patient images were qualitatively reviewed by one radiologist without a formal statistical analysis. These results suggested the proposed technique could correct motion-induced artifacts in the clinical setting. In addition, the conspicuity of susceptibility-related lesions using the proposed msEPI technique was comparable, or improved, compared to GRE. CONCLUSION: A 1-min full-brain T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted MRI technique was developed using msEPI with a navigator echo to correct motion-induced errors. Preliminary clinical results suggest faster scans and improved motion robustness and lesion conspicuity make msEPI a competitive alternative to traditional T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted MRI techniques for brain studies in the ED.

Low-Dose Whole Brain Radiation Therapy for Alzheimer's Dementia: Results From a Pilot Trial in Humans.

PURPOSE: We report neurocognitive, imaging, ophthalmologic, and safety outcomes following low-dose whole brain radiation therapy (LD-WBRT) for patients with early Alzheimer dementia (eAD) treated in a pilot trial. METHODS AND MATERIALS: Trial-enrolled patients were at least 55 years of age, had eAD meeting NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) Alzheimer's Criteria with confirmatory fluorodeoxyglucose and florbetapir positron emission tomography findings; had the capacity to complete neurocognitive function, psychological function, and quality-of-life assessments; had a Rosen modified Hachinski score ≤4; and had estimated survival >12 months. RESULTS: Five patients were treated with LD-WBRT (2 Gy × 5 over 1 week; 3 female; mean age, 73.2 years [range, 69-77]). Four of 5 patients had improved (n = 3) or stable (n = 1) Mini-Mental State Examination (second edition) T-scores at 1 year. The posttreatment scores of all 3 patients who improved increased to the average range. There were additional findings of stability of naming and other cognitive skills as well as stability to possible improvement in imaging findings. No safety issues were encountered. The only side effect was temporary epilation with satisfactory hair regrowth. CONCLUSIONS: Our results from 5 patients with eAD treated with LD-WBRT (10 Gy in 5 fractions) demonstrate a positive safety profile and provide preliminary, hypothesis-generating data to suggest that this treatment stabilizes or improves cognition. These findings will require further evaluation in larger, definitive, randomized trials.

Identification of single-dose, dual-echo based CBV threshold for fractional tumor burden mapping in recurrent glioblastoma.

Background: Relative cerebral blood volume (rCBV) obtained from dynamic susceptibility contrast (DSC) MRI is widely used to distinguish high grade glioma recurrence from post treatment radiation effects (PTRE). Application of rCBV thresholds yield maps to distinguish between regional tumor burden and PTRE, a biomarker termed the fractional tumor burden (FTB). FTB is generally measured using conventional double-dose, single-echo DSC-MRI protocols; recently, a single-dose, dual-echo DSC-MRI protocol was clinically validated by direct comparison to the conventional double-dose, single-echo protocol. As the single-dose, dual-echo acquisition enables reduction in the contrast agent dose and provides greater pulse sequence parameter flexibility, there is a compelling need to establish dual-echo DSC-MRI based FTB mapping. In this study, we determine the optimum standardized rCBV threshold for the single-dose, dual-echo protocol to generate FTB maps that best match those derived from the reference standard, double-dose, single-echo protocol. Methods: The study consisted of 23 high grade glioma patients undergoing perfusion scans to confirm suspected tumor recurrence. We sequentially acquired single dose, dual-echo and double dose, single-echo DSC-MRI data. For both protocols, we generated leakage-corrected standardized rCBV maps. Standardized rCBV (sRCBV) thresholds of 1.0 and 1.75 were used to compute single-echo FTB maps as the reference for delineating PTRE (sRCBV < 1.0), tumor with moderate angiogenesis (1.0 < sRCBV < 1.75), and tumor with high angiogenesis (sRCBV > 1.75) regions. To assess the sRCBV agreement between acquisition protocols, the concordance correlation coefficient (CCC) was computed between the mean tumor sRCBV values across the patients. A receiver operating characteristics (ROC) analysis was performed to determine the optimum dual-echo sRCBV threshold. The sensitivity, specificity, and accuracy were compared between the obtained optimized threshold (1.64) and the standard reference threshold (1.75) for the dual-echo sRCBV threshold. Results: The mean tumor sRCBV values across the patients showed a strong correlation (CCC = 0.96) between the two protocols. The ROC analysis showed maximum accuracy at thresholds of 1.0 (delineate PTRE from tumor) and 1.64 (differentiate aggressive tumors). The reference threshold (1.75) and the obtained optimized threshold (1.64) yielded similar accuracy, with slight differences in sensitivity and specificity which were not statistically significant (1.75 threshold: Sensitivity = 81.94%; Specificity: 87.23%; Accuracy: 84.58% and 1.64 threshold: Sensitivity = 84.48%; Specificity: 84.97%; Accuracy: 84.73%). Conclusions: The optimal sRCBV threshold for single-dose, dual-echo protocol was found to be 1.0 and 1.64 for distinguishing tumor recurrence from PTRE; however, minimal differences were observed when using the standard threshold (1.75) as the upper threshold, suggesting that the standard threshold could be used for both protocols. While the prior study validated the agreement of the mean sRCBV values between the protocols, this study confirmed that their voxel-wise agreement is suitable for reliable FTB mapping. Dual-echo DSC-MRI acquisitions enable robust single-dose sRCBV and FTB mapping, provide pulse sequence parameter flexibility and should improve reproducibility by mitigating variations in preload dose and incubation time.

Technical note: A spiral fluid-attenuated inversion recovery magnetic resonance imaging technique for stereotactic radiosurgery treatment planning for trigeminal neuralgia.

PURPOSE: Magnetic resonance imaging (MRI) is commonly used in treatment planning for stereotactic radiosurgery (SRS) of trigeminal neuralgia (TN). With current MRI techniques, the delineation of the trigeminal nerve root entry zone (REZ) may be degraded due to poor contrast and artifacts. The purpose of this work is to develop an MRI technique with better delineation of the trigeminal nerve REZ to improve SRS treatment planning for TN. METHODS: A spiral fluid-attenuated inversion recovery (FLAIR) MRI technique was developed to improve image quality by improving tissue contrast, fluid suppression, artifact reduction, and signal-to-noise ratio (SNR). A concomitant-phase compensation method based on spiral gradient waveforms was implemented to minimize artifacts due to magnetic field change induced by the metal frame used in Gamma Knife treatment planning. The image quality of spiral FLAIR was assessed in four healthy volunteers. The geometric accuracy was quantitatively evaluated by registering spiral FLAIR to computed tomography (CT) images and comparing it with existing MRI techniques. RESULTS: The spiral FLAIR technique demonstrated better delineation of the trigeminal nerve REZ, improved tissue contrast of the brain stem, and minimized flow artifacts, compared to steady-state free precession (SSFP) MRI. Spiral FLAIR also improved fluid suppression, SNR, and artifacts, which contributed to better delineation of the trigeminal nerve REZ compared to conventional Cartesian FLAIR. The measured mean (± standard deviation) distance between spiral FLAIR and CT images is 0.98 ± 0.56 mm, comparable to 0.40 ± 0.26 mm in 3T T1 spoiled gradient echo (T1-SPGR), 0.59 ± 0.25 mm in 3T SSFP, 0.66 ± 0.38 mm in 1.5T T1-SPGR, and 0.61 ± 0.25 mm in 1.5T Cartesian FLAIR. CONCLUSION: A spiral FLAIR technique with improved image quality and good geometric accuracy provides a potential alternative for treatment planning in SRS for TN patients.

Evaluation of single bolus, dual-echo dynamic susceptibility contrast MRI protocols in brain tumor patients.

Relative cerebral blood volume (rCBV) obtained from dynamic susceptibility contrast (DSC) MRI is adversely impacted by contrast agent leakage in brain tumors. Using simulations, we previously demonstrated that multi-echo DSC-MRI protocols provide improvements in contrast agent dosing, pulse sequence flexibility, and rCBV accuracy. The purpose of this study is to assess the in-vivo performance of dual-echo acquisitions in patients with brain tumors (n = 59). To verify pulse sequence flexibility, four single-dose dual-echo acquisitions were tested with variations in contrast agent dose, flip angle, and repetition time, and the resulting dual-echo rCBV was compared to standard single-echo rCBV obtained with preload (double-dose). Dual-echo rCBV was comparable to standard double-dose single-echo protocols (mean (standard deviation) tumor rCBV 2.17 (1.28) vs. 2.06 (1.20), respectively). High rCBV similarity was observed (CCC = 0.96), which was maintained across both flip angle (CCC = 0.98) and repetition time (CCC = 0.96) permutations, demonstrating that dual-echo acquisitions provide flexibility in acquisition parameters. Furthermore, a single dual-echo acquisition was shown to enable quantification of both perfusion and permeability metrics. In conclusion, single-dose dual-echo acquisitions provide similar rCBV to standard double-dose single-echo acquisitions, suggesting contrast agent dose can be reduced while providing significant pulse sequence flexibility and complementary tumor perfusion and permeability metrics.

Development of a spiral spin- and gradient-echo (spiral-SAGE) approach for improved multi-parametric dynamic contrast neuroimaging.

PURPOSE: The purpose of this study was to develop a spiral-based combined spin- and gradient-echo (spiral-SAGE) method for simultaneous dynamic contrast-enhanced (DCE-MRI) and dynamic susceptibility contrast MRI (DSC-MRI). METHODS: Using this sequence, we obtained gradient-echo TEs of 1.69 and 26 ms, a SE TE of 87.72 ms, with a TR of 1663 ms. Using an iterative SENSE reconstruction followed by deblurring, spiral-induced image artifacts were minimized. Healthy volunteer images are shown to demonstrate image quality using the optimized reconstruction, as well as for comparison with EPI-based SAGE. A bioreactor phantom was used to compare dynamic-contrast time courses with both spiral-SAGE and EPI-SAGE. A proof-of-concept cohort of patients with brain tumors shows the range of hemodynamic maps available using spiral-SAGE. RESULTS: Comparison of spiral-SAGE images with conventional EPI-SAGE images illustrates substantial reductions of image distortion and artifactual image intensity variations. Bioreactor phantom data show similar dynamic contrast time courses between standard EPI-SAGE and spiral-SAGE for the second and third echoes, whereas first-echo data show improvements in quantifying T1 changes with shorter echo times. In a cohort of patients with brain tumors, spiral-SAGE-based perfusion and permeability maps are shown with comparison with the standard single-echo EPI perfusion map. CONCLUSION: Spiral-SAGE provides a substantial improvement for the assessment of perfusion and permeability by mitigating artifacts typically encountered with EPI and by providing a shorter echo time for improved characterization of permeability. Spiral-SAGE enables quantification of perfusion, permeability, and vessel architectural parameters, as demonstrated in brain tumors.

Imaging of Neurotrauma in Acute and Chronic Settings.

Traumatic injuries of the brain and spinal cord are a significant source of mortality and long-term disability. A recent systematic study in a rat model of spinal cord injury (SCI) indicates severe, destructive, and very protracted inflammation as the key mechanism initiated by the massive injury involving the white matter. Although the severe inflammation is localized and counteracted by astrogliosis, it has a damaging effect on the blood vessels in the surrounding spinal cord, leading to persistent vasogenic edema. Evaluation of these injuries with imaging of the brain and spinal cord plays a crucial role in the acute trauma work-up, allowing clinicians to quickly identify abnormalities that require immediate medical or surgical intervention or to exclude them from the workup. Recently, anti-inflammatory agents have been shown to inhibit and accelerate the elimination of post-SCI inflammation in preclinical studies, and an exciting potential has arisen for the use of antiinflammatory drugs in clinical studies to achieve neuroprotection (i.e., inhibition of destruction caused by inflammation) and to inhibit vasogenic edema in SCI, traumatic brain injury, and stroke. In both subacute and chronic settings, imaging can guide therapy and provide important prognostic information. In this review, we discuss the imaging workup and evolving imaging findings of neurotrauma in the acute and chronic setting, including conventional and advanced imaging techniques. As neuroimaging is the primary mode of diagnostic analysis in neurotrauma, it is a critical component in future clinical trials evaluating neuroprotective therapies.

Incidental Finding of a Large Right Atrial Thrombus in a Patient With Cerebral Lymphoma.

Right atrial (RA) masses are rare, challenging to diagnose, and potentially life-threatening with high mortality if untreated. We present a patient presenting with diffuse large B-cell lymphoma in the brain that was incidentally found to have a large RA mass. For a better definition of the RA mass, extensive workup using multimodality imaging including chest computed tomography, transthoracic echocardiography, transesophageal echocardiography, cardiac magnetic resonance imaging, and left heart catheterization was warranted. The imaging demonstrated a large RA mass extending through the tricuspid valve into the right ventricle and superior and inferior vena cava without a mobile component. The mass was then successfully resected, and further histology examination was performed to rule out lymphoma and rare subtypes of diffuse large B-cell lymphoma. The comprehensive workup proved the RA mass to be a calcified thrombus rather than a direct metastatic spread of lymphoma.

Prolonged inflammation leads to ongoing damage after spinal cord injury.

The pathogenesis of spinal cord injury (SCI) remains poorly understood and treatment remains limited. Emerging evidence indicates that post-SCI inflammation is severe but the role of reactive astrogliosis not well understood given its implication in ongoing inflammation as damaging or neuroprotective. We have completed an extensive systematic study with MRI, histopathology, proteomics and ELISA analyses designed to further define the severe protracted and damaging inflammation after SCI in a rat model. We have identified 3 distinct phases of SCI: acute (first 2 days), inflammatory (starting day 3) and resolution (>3 months) in 16 weeks follow up. Actively phagocytizing, CD68+/CD163- macrophages infiltrate myelin-rich necrotic areas converting them into cavities of injury (COI) when deep in the spinal cord. Alternatively, superficial SCI areas are infiltrated by granulomatous tissue, or arachnoiditis where glial cells are obliterated. In the COI, CD68+/CD163- macrophage numbers reach a maximum in the first 4 weeks and then decline. Myelin phagocytosis is present at 16 weeks indicating ongoing inflammatory damage. The COI and arachnoiditis are defined by a wall of progressively hypertrophied astrocytes. MR imaging indicates persistent spinal cord edema that is linked to the severity of inflammation. Microhemorrhages in the spinal cord around the lesion are eliminated, presumably by reactive astrocytes within the first week post-injury. Acutely increased levels of TNF-alpha, IL-1beta, IFN-gamma and other pro-inflammatory cytokines, chemokines and proteases decrease and anti-inflammatory cytokines increase in later phases. In this study we elucidated a number of fundamental mechanisms in pathogenesis of SCI and have demonstrated a close association between progressive astrogliosis and reduction in the severity of inflammation.

Improving the image quality of 3D FLAIR with a spiral MRI technique.

PURPOSE: Fluid-attenuated inversion recovery (FLAIR) nulls the CSF signal and is widely used in neuro MRI exams. A 3D scan can provide high SNR, contiguous coverage, and reduced sensitivity to through-plane CSF flow. In this work, a 3D spiral FLAIR technique is proposed to improve the image quality of conventional 3D Cartesian FLAIR. METHODS: The 3D spiral FLAIR sequence incorporated a spiral-in/out readout to preserve higher scan efficiency and eliminate off resonance-induced artifacts observed with a commonly implemented spiral-out readout, a compensation approach to minimize phase errors due to the concomitant fields accompanying the spiral gradient, and an adapted variable flip angle scheme to preserve scan efficiency and maintain a long and stable echo train. 3D Cartesian and spiral FLAIR (~6 min each) were acquired on a 3 Tesla scanner from 6 subjects (age range: 31-64 years; mean: 39.5). Two neuroradiologists rated the images in a blinded fashion on a 5-point scale. The noise performance was assessed quantitatively. RESULTS: Compared to 3D Cartesian FLAIR, 3D spiral FLAIR exhibits greater reduction of artifacts from CSF, especially anterior to the brain stem (rated better in 4 cases), artifacts attributed to blood/flow in the deep brain (better or much better in all 6 cases), and superior overall image quality (much better in 5 cases) despite residual susceptibility artifacts near the nasal cavity. Quantitative assessment demonstrates ~1.5× higher average SNR than Cartesian data. CONCLUSION: 3D spiral FLAIR achieves higher SNR, reduced CSF, and blood/flow artifacts, providing an alternative to 3D Cartesian FLAIR for neurological exams.

Ten-year analysis of saccular aneurysms in the Barrow Ruptured Aneurysm Trial.

OBJECTIVE: The authors present the 10-year results of the Barrow Ruptured Aneurysm Trial (BRAT) for saccular aneurysms. The 1-, 3-, and 6-year results of the trial have been previously reported, as have the 6-year results with respect to saccular aneurysms. This final report comparing the safety and efficacy of clipping versus coiling is limited to an analysis of those patients presenting with subarachnoid hemorrhage (SAH) from a ruptured saccular aneurysm. METHODS: In the study, 362 patients had saccular aneurysms and were randomized equally to the clipping and the coiling cohorts (181 each). The primary outcome analysis was based on the assigned treatment group; poor outcome was defined as a modified Rankin Scale (mRS) score > 2 and was independently adjudicated. The extent of aneurysm obliteration was adjudicated by a nontreating neuroradiologist. RESULTS: There was no statistically significant difference in poor outcome (mRS score > 2) or deaths between these 2 treatment arms during the 10 years of follow-up. Of 178 clip-assigned patients with saccular aneurysms, 1 (< 1%) was crossed over to coiling, and 64 (36%) of the 178 coil-assigned patients were crossed over to clipping. After the initial hospitalization, 2 of 241 (0.8%) clipped saccular aneurysms and 23 of 115 (20%) coiled saccular aneurysms required retreatment (p < 0.001). At the 10-year follow-up, 93% (50/54) of the clipped aneurysms were completely obliterated, compared with only 22% (5/23) of the coiled aneurysms (p < 0.001). Two patients had documented rebleeding, both died, and both were in the assigned and treated coiled cohort (2/83); no patient in the clipped cohort (0/175) died (p = 0.04). In 1 of these 2 patients, the hemorrhage was not from the target aneurysm but from an incidental basilar artery aneurysm, which was coiled at the same time. CONCLUSIONS: There was no significant difference in clinical outcomes between the 2 assigned treatment groups as measured by mRS outcomes or deaths. Clinical outcomes in the patients with posterior circulation aneurysms were better in the coiling group at 1 year, but after 1 year this difference was no longer statistically significant. Rates of complete aneurysm obliteration and rates of retreatment favored patients who actually underwent clipping compared with those who underwent coiling.Clinical trial registration no.: NCT01593267 (clinicaltrials.gov).

Long-term outcome data from 121 patients treated with Gamma Knife stereotactic radiosurgery as salvage therapy for focally recurrent high-grade gliomas.

INTRODUCTION: We examined patient outcomes after Gamma Knife stereotactic radiosurgery (GKSRS) salvage therapy for recurrent high-grade gliomas (HGGs) to determine whether tumor grade or lesion size affected overall survival (OS) and progression-free survival (PFS). METHODS: This single-center retrospective study assessed radiographic response and clinical outcomes following GKSRS salvage treatment of recurrent malignant gliomas (January 2005-March 2014). RESULTS: A total of 121 patients (67 female) with 132 tumors were treated. Median (range) PFS was 4.7 (3.9-5.4) months for the cohort, 6.8 (4.6-8.9) months for initial grade 2 tumors, 4.2 (1.9-6.5) months for initial grade 3 tumors, and 4.3 (3.7-4.9) months for initial grade 4 tumors. Patients with small lesions (≤6.7 cm3; n = 53) had significantly longer median (range) PFS (6.8 [4.8-8.8], P=0.02). CONCLUSIONS: GKSRS offers meaningful salvage therapy with minimal morbidity in appropriately selected patients with focally recurrent HGGs.

Procedural Variables Influencing Stereotactic Accuracy and Efficiency in Deep Brain Stimulation Surgery.

BACKGROUND: Deep brain stimulation (DBS) is well-established, evidence-based therapy for Parkinson disease, essential tremor, and primary dystonia. Clinical outcome studies have recently shown that "asleep" DBS lead placement, performed using intraoperative imaging with stereotactic accuracy as the surgical endpoint, has motor outcomes comparable to traditional "awake" DBS using microelectrode recording (MER), but with shorter case times and improved speech fluency. OBJECTIVE: To identify procedural variables in DBS surgery associated with improved surgical efficiency and stereotactic accuracy. METHODS: Retrospective review of 323 cases with 546 leads placed (August 2011-October 2014). In 52% (n = 168) of cases, patients were asleep under general anesthesia without MER. Multivariate regression identified independent predictors of reduced surgery time and improved stereotactic accuracy. RESULTS: MER was an independent contributor to increased procedure time (+44 min; P = .03). Stereotactic accuracy was better in asleep patients. Accuracy was improved with frame-based stereotaxy at head of bed 0° vs frameless stereotaxy at head of bed 30°. Improved accuracy was also associated with shorter procedures (r = 0.17; P = .049). Vector errors were evenly distributed around the planned target for the globus pallidus internus, but directionally skewed for the subthalamic (medial-posterior) and ventral intermediate nuclei (medial-anterior). CONCLUSION: Distinct procedural variables in DBS surgery are associated with reduced case times and improved stereotactic accuracy.

A 2D spiral turbo-spin-echo technique.

PURPOSE: 2D turbo-spin-echo (TSE) is widely used in the clinic for neuroimaging. However, the long refocusing radiofrequency pulse train leads to high specific absorption rate (SAR) and alters the contrast compared to conventional spin-echo. The purpose of this work is to develop a robust 2D spiral TSE technique for fast T2 -weighted imaging with low SAR and improved contrast. METHODS: A spiral-in/out readout is incorporated into 2D TSE to fully take advantage of the acquisition efficiency of spiral sampling while avoiding potential off-resonance-related artifacts compared to a typical spiral-out readout. A double encoding strategy and a signal demodulation method are proposed to mitigate the artifacts because of the T2 -decay-induced signal variation. An adapted prescan phase correction as well as a concomitant phase compensation technique are implemented to minimize the phase errors. RESULTS: Phantom data demonstrate the efficacy of the proposed double encoding/signal demodulation, as well as the prescan phase correction and concomitant phase compensation. Volunteer data show that the proposed 2D spiral TSE achieves fast scan speed with high SNR, low SAR, and improved contrast compared to conventional Cartesian TSE. CONCLUSION: A robust 2D spiral TSE technique is feasible and provides a potential alternative to conventional 2D Cartesian TSE for T2 -weighted neuroimaging.

Improving the utility of 1H-MRS for the differentiation of glioma recurrence from radiation necrosis.

Proton magnetic resonance spectroscopy (1H-MRS) has shown promise in distinguishing recurrent high-grade glioma from posttreatment radiation effect (PTRE). The purpose of this study was to establish objective 1H-MRS criteria based on metabolite peak height ratios to distinguish recurrent tumor (RT) from PTRE. A retrospective analysis of magnetic resonance imaging and 1H-MRS data was performed. Spectral metabolites analyzed included N-acetylaspartate, choline (Cho), creatine (Cr), lactate (Lac), and lipids (Lip). Quantitative 1H-MRS criteria to differentiate RT from PTRE were identified using 81 biopsy-matched spectral voxels. A receiver operating characteristic curve analysis was conducted for all metabolite ratio combinations with the pathology diagnosis as the classification variable. Forward discriminant analysis was used to identify ratio variables that maximized the correct classification of RT versus PTRE. Our results were applied to 205 records without biopsy-matched voxels to examine the percent agreement between our criteria and the radiologic diagnoses. Five ratios achieved an acceptable balance [area under the curve (AUC) ≥ 0.700] between sensitivity and specificity for distinguishing RT from PTRE, and each ratio defined a criterion for diagnosing RT. The ratios are as follows: Cho/Cr > 1.54 (sensitivity 66%, specificity 79%), Cr/Cho ≤ 0.63 (sensitivity 65%, specificity 79%), Lac/Cho ≤ 2.67 (sensitivity 85%, specificity 58%), Lac/Lip ≤ 1.64 (sensitivity 54%, specificity 95%), and Lip/Lac > 0.58 (sensitivity 56%, specificity 95%). Application of our ratio criteria in prospective studies may offer an alternative to biopsy or visual spectral pattern recognition to distinguish RT from PTRE in patients with gliomas.

Radiogenomics to characterize regional genetic heterogeneity in glioblastoma.

BACKGROUND: Glioblastoma (GBM) exhibits profound intratumoral genetic heterogeneity. Each tumor comprises multiple genetically distinct clonal populations with different therapeutic sensitivities. This has implications for targeted therapy and genetically informed paradigms. Contrast-enhanced (CE)-MRI and conventional sampling techniques have failed to resolve this heterogeneity, particularly for nonenhancing tumor populations. This study explores the feasibility of using multiparametric MRI and texture analysis to characterize regional genetic heterogeneity throughout MRI-enhancing and nonenhancing tumor segments. METHODS: We collected multiple image-guided biopsies from primary GBM patients throughout regions of enhancement (ENH) and nonenhancing parenchyma (so called brain-around-tumor, [BAT]). For each biopsy, we analyzed DNA copy number variants for core GBM driver genes reported by The Cancer Genome Atlas. We co-registered biopsy locations with MRI and texture maps to correlate regional genetic status with spatially matched imaging measurements. We also built multivariate predictive decision-tree models for each GBM driver gene and validated accuracies using leave-one-out-cross-validation (LOOCV). RESULTS: We collected 48 biopsies (13 tumors) and identified significant imaging correlations (univariate analysis) for 6 driver genes: EGFR, PDGFRA, PTEN, CDKN2A, RB1, and TP53. Predictive model accuracies (on LOOCV) varied by driver gene of interest. Highest accuracies were observed for PDGFRA (77.1%), EGFR (75%), CDKN2A (87.5%), and RB1 (87.5%), while lowest accuracy was observed in TP53 (37.5%). Models for 4 driver genes (EGFR, RB1, CDKN2A, and PTEN) showed higher accuracy in BAT samples (n = 16) compared with those from ENH segments (n = 32). CONCLUSION: MRI and texture analysis can help characterize regional genetic heterogeneity, which offers potential diagnostic value under the paradigm of individualized oncology.

Sliding-slab three-dimensional TSE imaging with a spiral-In/Out readout.

PURPOSE: T2 -weighted imaging is of great diagnostic value in neuroimaging. Three-dimensional (3D) Cartesian turbo spin echo (TSE) scans provide high signal-to-noise ratio (SNR) and contiguous slice coverage. The purpose of this preliminary work is to implement a novel 3D spiral TSE technique with image quality comparable to 2D/3D Cartesian TSE. METHODS: The proposed technique uses multislab 3D TSE imaging. To mitigate the slice boundary artifacts, a sliding-slab method is extended to spiral imaging. A spiral-in/out readout is adopted to minimize the artifacts that may be present with the conventional spiral-out readout. Phase errors induced by B0 eddy currents are measured and compensated to allow for the combination of the spiral-in and spiral-out images. A nonuniform slice encoding scheme is used to reduce the truncation artifacts while preserving the SNR performance. RESULTS: Preliminary results show that each of the individual measures contributes to the overall performance, and the image quality of the results obtained with the proposed technique is, in general, comparable to that of 2D or 3D Cartesian TSE. CONCLUSION: 3D sliding-slab TSE with a spiral-in/out readout provides good-quality T2 -weighted images, and, therefore, may become a promising alternative to Cartesian TSE.