Time-course assessment of 3D-image distortion on the 1.5 T Marlin/Elekta Unity MR-LINAC.

PURPOSE: The efficacy of MR-guided radiotherapy on a MR-LINAC (MR-L) is dependent on the geometric accuracy of its MR images over clinically relevant Fields-of-View (FOVs). Our objectives were to: evaluate gradient non-linearity (GNL) on the Elekta Unity MR-L across time via 76 weekly measurements of 3D-distortion over concentrically larger diameter spherical volumes (DSVs); quantify distortion measurement error; and assess the temporal stability of spatial distortion using statistical process control (SPC). METHODS: MR-image distortion was assessed using a large-FOV 3D-phantom containing 1932 markers embedded in seven parallel plates, spaced 25 mm × 25 mm in- and 55 mm through-plane. Automatically analyzed T1 images yielded distortions in 200, 300, 400 and 500 mm concentric DSVs. Distortion measurement error was evaluated using median absolute difference analysis of imaging repeatability tests. RESULTS: Over the measurement period absolute time-averaged distortion varied between: dr = 0.30 - 0.49 mm, 0.53 - 0.80 mm, 1.0 - 1.4 mm and 2.28 - 2.37 mm, for DSVs 200, 300, 400 and 500 mm at the 98th percentile level. Repeatability tests showed that imaging/repositioning introduces negligible error: mean ≤ 0.02 mm (max ≤ 0.3 mm). SPC analysis showed image distortion was stable across all DSVs; however, noticeable changes in GNL were observed following servicing at the one-year mark. CONCLUSIONS: Image distortion on the MR-L is in the sub-millimeter range for DSVs ≤ 300 mm and stable across time, with SPC analysis indicating all measurements remain within control for each DSV.

Clinicopathologic and Treatment Features of Long-Term Surviving Brain Metastasis Patients.

BACKGROUND: The purpose of our study was to characterize clinical features among brain metastasis (BM) patients who were long term survivors (LTS). METHODS: We reviewed a registry of BM patients referred to our multidisciplinary BM clinic between 2006 and 2014 and identified 97 who lived ≥ 3 years following BM diagnosis. The clinical and treatment characteristics were obtained from a prospectively maintained database, and additional information was obtained through review of electronic medical records and radiologic images. Survival analyses were performed using the Kaplan-Meier method. RESULTS: Median follow up for LTS was 67 months (range 36-181). Median age was 54 years, 65% had single BM, 39% had stable extracranial disease at the time of BM treatment, and brain was the first site of metastasis in 76%. Targetable mutations were present in 39% of patients and 66% received treatment with targeted-, hormonal-, or immuno-therapy. Brain surgery at the time of diagnosis was performed in 40% and stereotactic radiosurgery (SRS) or whole brain radiotherapy (alone or combination) in 52% and 56%, respectively. Following initial BM treatment, 5-year intracranial disease-free survival was 39%, and the cumulative incidence of symptomatic radio-necrosis was 16%. Five and ten-year overall survival was 72% and 26%, respectively. CONCLUSION: Most LTS were younger than 60 years old and had a single BM. Many received treatment with surgery or targeted, immune, or hormonal therapy.

Neurological Death is Common in Patients With EGFR Mutant Non-Small Cell Lung Cancer Diagnosed With Brain Metastases.

PURPOSE: Brain metastases (BrM) are common in patients with epidermal growth factor receptor (EGFRm) mutant non-small cell lung cancer (NSCLC). We sought to determine the rate of neurologic death (ND) in this population. METHODS AND MATERIALS: We analyzed data from 198 patients who received a diagnosis of BrM from EGFRm NSCLC between 2004 and 2016, comparing patients whose initial treatment for BrM was stereotactic radiosurgery with or without tyrosine kinase inhibitors (TKI), whole brain radiation therapy (WBRT) with or without TKI, or TKI alone. The incidence of ND was determined using a competing risks analysis. Univariate and multivariate analyses were used to identify clinical variables associated with this outcome. RESULTS: The percentage of patients who initially received stereotactic radiosurgery, whole brain radiation therapy, or TKI alone was 22%, 61%, and 17%, respectively. Median overall survival in these subgroups was 31.1, 14.6, and 24.6 months, respectively (P = .0016). The 5-year incidence of ND among all patients was 40% and did not significantly vary according to treatment group. In a multivariable model, only leptomeningeal disease at any point in a patient's disease course significantly correlated with ND (hazard ratio 4.75, P <.001). CONCLUSIONS: Among our cohort of patients with BrM from EGFRm NSCLC, the incidence of ND was significantly higher than suggested by previous reports. BrM should be considered a driver of mortality in many patients with EGFRm NSCLC, and treatments providing better control of BrM, lower neurocognitive side effects, and maintenance of quality of life are needed.

Influence of hepatitis C virus on neurocognitive function in patients free from other risk factors: validation from therapeutic outcomes.

BACKGROUND AND AIMS: Mild neurocognitive dysfunction and altered cerebral proton magnetic resonance spectroscopy ((1) H-MRS) have been demonstrated in patients with chronic hepatitis C (CHC). This longitudinal study aimed to quantify these abnormalities in a cohort of patients free from correlated risk factors and determine whether treatment-induced viral clearance abolished these abnormalities. METHODS: Treatment-naïve, non-cirrhotic patients with CHC, rigorously screened and excluded for other causes of impaired neurocognition, underwent neurocognitive testing, (1) H-MRS and evaluation for quality of life (QOL), mood and fatigue, before and 6 months after the completion of antiviral therapy. A comparison group of healthy controls was similarly assessed at baseline and 1 year later. RESULTS: Post-treatment results in 40 patients with CHC [31 sustained virological responders, hepatitis C virus (HCV)-R and 9 non-responders, HCV-NR] were compared with their pretreatment results, and with the baseline and follow-up assessments of 39 healthy controls. Before receiving treatment, patients had impaired learning efficiency, poorer QOL and higher fatigue scores compared with the controls. Viral clearance was associated with a significant albeit small improvement in the QOL score that did not reach control levels. Cerebral (1) H-MRS demonstrated a lower N-acetyl aspartate/creatine (CRE) ratio in the globus pallidus (GP) of patients with hepatitis C, which was unchanged with viral clearance. The GP choline/CRE ratio increased in HCV-R following treatment, without a correlation with cognitive measures. CONCLUSIONS: The hepatitis C virus has a measurable effect on CNS integrity in patients screened for other medical and/or psychiatric comorbidities. Viral clearance has not been demonstrated to abolish these abnormalities.

3D MR-spectroscopic imaging assessment of metabolic activity in the prostate during the PSA "bounce" following 125iodine brachytherapy.

PURPOSE: A temporary increase in prostate-specific antigen (PSA) values is observed in 30%-40% of men following (125)I brachytherapy (BT) for prostate cancer. We present the results of a study to characterize prostate metabolic activity during the PSA "bounce" and to correlate metabolic changes with PSA levels using three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI). METHODS AND MATERIALS: 3D-MRSI was performed in 24 patients during the PSA bounce. Eight of these had also had a baseline 3D-MRSI scan before BT for the purpose of tumor mapping. The 3D-MRSI was repeated at 6- and 12-month intervals, and PSA levels were monitored every 3 months. Twenty-one of the patients had favorable-risk prostate cancer, and 3 had intermediate risk. RESULTS: The choline+creatine signal intensity, although markedly reduced, was observable following BT. Diffuse activity not corresponding to original biopsy-positive sites was observed in 22 cases, and 2 cases were documented to have local recurrence. No statistically significant correlation between metabolic activity and PSA levels at each interval was found. CONCLUSION: Post-BT prostate 3D-MRSI shows evidence of diffuse metabolic activity unrelated to residual malignancy. This supports the benign nature of the PSA bounce and suggests an inflammatory etiology. In the situation of a rising PSA, observation of focal activity on MRI/3D-MRSI could be a useful adjunct to suggest local recurrence at an earlier interval after brachytherapy when prostate biopsies would still be unhelpful. Longer follow-up is necessary to confirm the complex relationship between metabolic activity and PSA levels.

Assessment of metabolite quantitation reproducibility in serial 3D-(1)H-MR spectroscopic imaging of human brain using stereotactic repositioning.

Intrasubject reproducibility of metabolite quantitation in three-dimensional proton magnetic resonance spectroscopic imaging (3D-MRSI) was investigated in 10 healthy volunteers over five separate sessions using two echo times (TEs): 144 and 30 ms. The use of a Gill-Thomas-Cosman (GTC) stereotactic head frame enabled precise subject repositioning and immobilization. Metabolite levels from each voxel in the volume of interest (VOI) were quantified using the Linear Combination of Model spectra (LCModel) analysis algorithm, and coefficients of variation (CVs) were calculated. Standard error estimates (%SD or Cramer-Rao lower bounds) generated by LCModel were used as a confidence filter. The 95% confidence interval (CI) was found for each metabolite, providing an indication of the normal fluctuation expected for 3D-MRSI. In vivo, median CVs at the %SD < or = 20 level were found to be (%CV for TE = 144 and 30 ms, respectively): N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (NAA): 10.2% and 13.5%; creatine plus phosphocreatine (Cr), 14.4% and 21.7%; and choline-containing compounds (Cho), 15.2% and 18.4%. Relaxing the statistical filtering criteria to %SD < or = 30 increased median CVs by less than 5% and permitted in vivo quantitation reproducibility to be evaluated for glutamine plus glutamate (Glx) and myoinositol (Ins) for TE = 30 ms, yielding CVs of 24.0% and 21.0%, respectively.

Characterization of proteoglycan depletion in articular cartilage using two-dimensional time domain nuclear magnetic resonance.

In vitro proteoglycan (PG) depletion in the 20-40% range (enzymatic PG depletion of normal cartilage in the early osteoarthritis (OA) PG depletion range) was investigated in articular cartilage using 2D time domain NMR relaxation techniques. Spin-lattice relaxation times were measured at low fields (T(1rho)) and at high fields (T(1)) using nonselective and selective excitation pulse sequences. The short relaxation time magnetization components in T(1rho) ( approximately 8% signal) and nonselective T(1) ( approximately 5% signal) experiments were significantly altered with PG degradation. In addition, a magnetization component ( approximately 5% signal) with a "fast " T(1) approximately 7 ms was observed in the T(1) experiment involving selective excitation. This fast T(1) was at least 10 times shorter than the short T(1) in the nonselective experiment and was associated with a strong magnetization exchange mechanism between collagen and PG. The results suggest that T(1rho) and T(1) (nonselective and selective) relaxation based MRI techniques, which focus on the short relaxation time magnetization components, have the potential of detecting molecular abnormalities associated with early OA earlier than single, long relaxation time component approaches.

Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors.

Neurocognitive morbidity has been reported in individuals with chronic hepatitis C virus (HCV) infection, but the magnitude of such dysfunction in the absence of disease-correlated factors known to affect the central nervous system (e.g., substance abuse, cirrhosis, depression, interferon treatment) and the impact of any such change on functioning is unclear. We investigated a cohort of individuals with HCV, all of whom were carefully screened to exclude relevant comorbidities, to elucidate virus-related changes in the brain using neuropsychological tests and magnetic resonance spectroscopy (MRS). A cohort of 37 patients with chronic HCV infection was culled from 300 consecutive patients presenting to a tertiary care liver clinic. A comparison group of healthy controls (n = 46) was also assessed. Of 10 neurocognitive measures evaluated, the HCV group showed marginally poorer learning efficiency compared with controls; only 13% of patients demonstrated a clinical level of impairment on this test (defined as 1.5 SD below the normative standard). Although patients reported greater levels of fatigue and symptoms of depression, these factors did not correlate with the degree of learning inefficiency. With respect to MRS, the HCV group demonstrated increased choline and reduced N-acetyl aspartate relative to controls in the central white matter. Indicators of liver disease severity did not correlate with either memory or MRS abnormalities. In conclusion, while our findings support an association between hepatitis C and indicators of central nervous system involvement in a cohort of patients carefully screened to eliminate other factors influencing neurocognitive integrity, the clinical significance of these effects is limited.