Contrast-enhancing Lesion Volume Research Articles

Automated segmentation of ablated lesions using deep convolutional neural networks: A basis for response assessment following laser interstitial thermal therapy.

Laser interstitial thermal therapy (LITT) of intracranial tumors or radiation necrosis enables tissue diagnosis, cytoreduction, and rapid return to systemic therapies. Ablated tissue remains in situ, resulting in characteristic post-LITT edema associated with transient clinical worsening and complicating post-LITT response assessment. All patients receiving LITT at a single center for tumors or radiation necrosis from 2015 to 2023 with ≥9 months of MRI follow-up were included. An nnU-Net segmentation model was trained to automatically segment contrast-enhancing lesion volume (CeLV) of LITT-treated lesions on T1-weighted images. Response assessment was performed using volumetric measurements. Three hundred and eighty four unique MRI exams of 61 LITT-treated lesions and 6 control cases of medically managed radiation necrosis were analyzed. Automated segmentation was accurate in 367/384 (95.6%) images. CeLV increased to a median of 68.3% (IQR 35.1-109.2%) from baseline at 1-3 months from LITT (P = 0.0012) and returned to baseline thereafter. Overall survival (OS) for LITT-treated patients was 39.1 (9.2-93.4) months. Lesion expansion above 40% from volumetric nadir or baseline was considered volumetric progression. Twenty-one of 56 (37.5%) patients experienced progression for a volumetric progression-free survival of 21.4 (6.0-93.4) months. Patients with volumetric progression had worse OS (17.3 vs 62.1 months, P = 0.0015). Post-LITT CeLV expansion is quantifiable and resolves within 6 months of LITT. Development of response assessment criteria for LITT-treated lesions is feasible and should be considered for clinical trials. Automated lesion segmentation could speed the adoption of volumetric response criteria in clinical practice.

Predictive IDH Genotyping Based on the Evaluation of Spatial Metabolic Heterogeneity by Compartmental Uptake Characteristics in Preoperative Glioma Using 18F-FET PET.

Molecular markers are of increasing importance for classifying, treating, and determining the prognosis for central nervous system tumors. Isocitrate dehydrogenase (IDH) is a critical regulator of glucose and amino acid metabolism. Our objective was to investigate metabolic reprogramming of glioma using compartmental uptake (CU) characteristics in O-(2-18F-fluoroethyl)-l-tyrosine (FET) PET and to evaluate its diagnostic potential for IDH genotyping. Methods: Between 2017 and 2022, patients with confirmed glioma were preoperatively investigated using static 18F-FET PET. Metabolic tumor volume (MTV), MTV for 60%-100% uptake (MTV60), and T2-weighted and contrast-enhancing lesion volumes were automatically segmented using U-Net neural architecture and isocontouring. Volume intersections were determined using the Dice coefficient. Uptake characteristics were determined for metabolically defined compartments (central [80%-100%] and peripheral [60%-75%] areas of 18F-FET uptake). CU ratio was defined as the fraction between the peripheral and central compartments. Mean target-to-background ratio was calculated. Comparisons were performed using parametric and nonparametric tests. Receiver-operating-characteristic curves, regression, and correlation were used for statistical analysis. Results: In total, 52 participants (male, 27, female, 25; mean age ± SD, 51 ± 16 y) were evaluated. MTV60 was greater and distinct from contrast-enhancing lesion volume (P = 0.046). IDH-mutated tumors presented a greater volumetric CU ratio and SUV CU ratio than IDH wild-type tumors (P < 0.05). Volumetric CU ratio determined IDH genotype with excellent diagnostic performance (area under the curve [AUC], 0.88; P < 0.001) at more than 5.49 (sensitivity, 86%, specificity, 90%), because IDH-mutated tumors presented a greater peripheral metabolic compartment than IDH wild-type tumors (P = 0.045). MTV60 and MTV were not suitable for IDH classification (P > 0.05). SUV CU ratio (AUC, 0.72; P = 0.005) and target-to-background ratio (AUC, 0.68; P = 0.016) achieved modest diagnostic performance-inferior to the volumetric CU ratio. Furthermore, the classification of loss of heterozygosity of chromosomes 1p and 19q (AUC, 0.75; P = 0.019), MGMT promoter methylation (AUC, 0.70; P = 0.011), and ATRX loss (AUC, 0.73; P = 0.004) by amino acid PET was evaluated. Conclusion: We proposed parametric 18F-FET PET as a noninvasive metabolic biomarker for the evaluation of CU characteristics, which differentiated IDH genotype with excellent diagnostic performance, establishing a critical association between spatial metabolic heterogeneity, mitochondrial tricarboxylic acid cycle, and genomic features with critical implications for clinical management and the diagnostic workup of patients with central nervous system cancer.

SURG-09. Benefits of laser interstitial thermal therapy in the treatment of biopsy-proven radiation necrosis

IntroductionLaser interstitial thermal therapy (LITT) is a minimally-invasive treatment option often used for patients with deep-seated intracranial lesions. It has been implemented as a definitive treatment for radiation necrosis (RN), which occurs in 9–14% of patients after stereotactic radiosurgery (SRS) for brain metastases (BM). Medical management (MM) with steroids is a common first-line therapy, with variable response and numerous side effects, especially regarding immunotherapy.MethodsPatients with biopsy-proven RN after SRS for BM who received LITT or MM at two academic centers were retrospectively reviewed. Treatment failure was defined as radiographic progression that necessitated a change in management. Measurements of total (TLV) and contrast-enhancing lesion volume (ceLV) were obtained from MRI by semi-automated analysis using the BrainLab iPlan Cranial 3.0 software.ResultsSeventy-two patients were followed for 10.0 (4.2–25.1) months and 57 (79%) received LITT. Steroid cessation occurred at a median of 37 days post-LITT compared to 245 days after MM (p<0.01). On Kaplan-Meier analyses, there was no significant difference between the two groups in overall survival (LITT median of 15.2 months vs 11.6 months, p = 0.60) or freedom from local progression (13.6 months vs. 7.06 months), though LITT trended to show a benefit in both metrics. When controlled for follow-up duration, patients treated with LITT were three times more likely to be weaned off steroids prior to the study endpoint compared to those who were medically managed (p=0.003). The LITT cohort demonstrated a general radiographic trend of initially increased CeLV followed by contraction, with significant decreases from pre-operative at 10–12 months (p<0.01). The MM group did not demonstrate any statistically significant radiographic trends.ConclusionThese results suggest that LITT for RN significantly reduces the time to steroid cessation and characterize a stereotyped radiographic response to LITT. Future prospective studies will be important to their validation.

Combined Transarterial Embolization and Percutaneous Sclerotherapy as Treatment for Refractory and Nonresectable Aneurysmal Bone Cysts

PurposeTo evaluate the safety and effectiveness of combined transarterial embolization and percutaneous sclerotherapy in the treatment of refractory and nonresectable aneurysmal bone cysts (ABCs) as assessed by imaging and clinical outcomes. Materials and MethodsThis retrospective, single-center study included 16 consecutive patients (9 women and 7 men; median age, 17 years [range, 6–25 years]) who underwent combined transarterial embolization (using ethylene vinyl alcohol) and percutaneous sclerotherapy (using ethanol gel and polidocanol) for refractory and nonresectable ABCs. The median follow-up was 27.3 months (range, 6.7–47.5 months). Grade of mineralization (5-point Likert scale), grade of fluid-fluid levels (FFLs; 4-point Likert scale), and contrast-enhancing lesion volume were evaluated before and after treatment. The quality of life was determined before and after treatment using the Musculoskeletal Tumor Society (MSTS) score and the 36-Item Short Form Survey (SF-36) health questionnaire. ResultsA mean of 1.6 ± 0.7 transarterial embolizations and 3.2 ± 1.7 percutaneous sclerotherapies were performed. No adverse events were observed. All patients showed either partial or complete response; no patient showed ABC recurrence. The grade of mineralization (3.7 ± 0.7 after therapy vs 1.4 ± 0.5 at baseline; P < .0001) and grade of FFL (3.5 ± 0.8 after therapy vs 1.9 ± 0.6 at baseline; P < .0001) significantly improved after therapy compared with baseline. The mean contrast-enhancing lesion volume significantly decreased after treatment compared with baseline (45.9 mm³ ± 96.1 vs 156.0 mm³ ± 115.3, respectively; P = .0003). The MSTS scores (28.8 ± 1.8 after treatment vs 14.1 ± 8.6 at baseline; P < .0001) and SF-36 findings revealed a significant improvement in the quality of life after treatment compared with baseline, leaving most patients without relevant constraints. ConclusionsCombined transarterial embolization and percutaneous sclerotherapy is a minimally invasive, safe, and effective treatment option for refractory and nonresectable ABCs. Treatment fostered bone mineralization and significantly improved patients’ quality of life.

INNV-02. RADIOGRAPHIC CHARACTERISTICS AND STEROID USAGE IN LASER INTERSTITIAL THERMAL THERAPY VERSUS MEDICAL MANAGEMENT FOR BIOPSY-PROVEN RADIATION NECROSIS AFTER STEREOTACTIC RADIOSURGERY OF BRAIN METASTASES

Abstract INTRODUCTION Radiation necrosis (RN) occurs in 9–14% of patients after stereotactic radiosurgery (SRS) for brain metastases (BM). Medical management (MM) with steroids is a common first-line therapy, with variable response and numerous side effects, especially regarding immunotherapy. Laser interstitial thermal therapy (LITT) has been introduced as an efficacious, steroid-reducing alternative, however limited data exists comparing LITT to MM. METHODS Patients with biopsy-proven RN after SRS for BM who received LITT or MM at two academic centers were retrospectively reviewed. Treatment failure was defined as radiographic progression that necessitated a change in management. Measurements of total (TLV) and contrast-enhancing lesion volume (ceLV) were obtained from MRI by semi-automated analysis using the BrainLab iPlan Cranial 3.0 software. RESULTS Eighty-one patients were followed for 11.7 (4.3–27.0) months and 57 (70%) received LITT. Steroid cessation occurred at a median of 37 days post-LITT compared to 162 days after MM (p&amp;lt; 0.01). Treatment failure occurred in 5% of LITT patients at 4.0 (3.2–4.8) months and 13% of MM patients at 4.4 (4.1–5.3) months (p &amp;gt;0.05). Patients were 3.2 times more likely to be weaned off steroids when treated with LITT compared to MM (p&amp;lt; 0.01), when controlled for age, pre-operative ceLV, and post-operative seizure on multivariate analysis. Both groups demonstrated decreasing TLV and ceLV between baseline and last follow-up MRI. At 6–9 months, the LITT cohort demonstrated a -59% change in ceLV compared to -7% with MM (p &amp;gt;0.05). The LITT cohort demonstrated a significant decrease in ceLV between scans at 0–2 and 6–9 months (p&amp;lt; 0.01). The MM group did not demonstrate a statistically significant decrease in ceLV until 12 months. CONCLUSION This study suggests that LITT for RN significantly reduces the time to steroid cessation, and earlier radiographic response to treatment by LITT. Large, prospective trials are needed to validate these findings.

Detection of Monocyte/Macrophage and Microglia Activation in the TMEV Model of Chronic Demyelination Using USPIO-Enhanced Ultrahigh-Field Imaging.

Blood-derived monocytes/macrophages can be labeled with ultrasmall superparamagnetic iron oxides (USPIO) at periphery and subsequently migrate into areas of inflammation in the brain. We investigated temporal pattern of migration of peripheral immune cells in Theiler's murine encephalomyelitis virus (TMEV) model of chronic demyelination by USPIO-enhanced imaging. Fifteen SJL mice (Envigo, Indianapolis, IN) were injected with TMEV (n = 12) or saline (n = 3) at 7 weeks of age. Brain MRI of 9.4 T was performed at 3 months postinfection (mpi) (the peak of inflammatory phase), at 4, 5, and 7 mpi (throughout neurodegenerative phase) using T2*-weighted gradient echo MRI, and performed 24 hours after USPIO injection. Contrast enhancing lesion (CEL) number and volume were measured and development of brain atrophy was assessed across serial time points. Clinical disability scale and rotarod score assessed disease progression. CEL was detected in a total of eight (66.7%) TMEV-infected animals and none of the Controls. The CEL was present in four (33.3%) TMEV-infected animals at 3 mpi, two (16.7%) at 4 mpi, six (54.5%) at 5 mpi, and four (44.4%) at 7 mpi, respectively. In TMEV-infected animals, the CEL number and volume increased significantly from 3 to 7 mpi (P < .01 for both). The correlation between total CEL number and volume with clinical and MRI outcomes was trending (P < .05). On histopathology analysis, CEL showed increased density of Iba1 staining for microglia activity. Serial USPIO imaging is a promising biomarker for investigating the effect of therapeutic interventions on monocytes/macrophages and microglia activation and neurodegeneration in TMEV-infected animals.

Perfusion MRI-Based Fractional Tumor Burden Differentiates between Tumor and Treatment Effect in Recurrent Glioblastomas and Informs Clinical Decision-Making.

Fractional tumor burden better correlates with histologic tumor volume fraction in treated glioblastoma than other perfusion metrics such as relative CBV. We defined fractional tumor burden classes with low and high blood volume to distinguish tumor from treatment effect and to determine whether fractional tumor burden can inform treatment-related decision-making. Forty-seven patients with high-grade gliomas (primarily glioblastoma) with recurrent contrast-enhancing lesions on DSC-MR imaging were retrospectively evaluated after surgical sampling. Histopathologic examination defined treatment effect versus tumor. Normalized relative CBV thresholds of 1.0 and 1.75 were used to define low, intermediate, and high fractional tumor burden classes in each histopathologically defined group. Performance was assessed with an area under the receiver operating characteristic curve. Consensus agreement among physician raters reporting hypothetic changes in treatment-related decisions based on fractional tumor burden was compared with actual real-time treatment decisions. Mean lower fractional tumor burden, high fractional tumor burden, and relative CBV of the contrast-enhancing volume were significantly different between treatment effect and tumor (P = .002, P < .001, and P < .001), with tumor having significantly higher fractional tumor burden and relative CBV and lower fractional tumor burden. No significance was found with intermediate fractional tumor burden. Performance of the area under the receiver operating characteristic curve was the following: high fractional tumor burden, 0.85; low fractional tumor burden, 0.7; and relative CBV, 0.81. In comparing treatment decisions, there were disagreements in 7% of tumor and 44% of treatment effect cases; in the latter, all disagreements were in cases with scattered atypical cells. High fractional tumor burden and low fractional tumor burden define fractions of the contrast-enhancing lesion volume with high and low blood volume, respectively, and can differentiate treatment effect from tumor in recurrent glioblastomas. Fractional tumor burden maps can also help to inform clinical decision-making.

Moving Toward a Consensus DSC-MRI Protocol: Validation of a Low-Flip Angle Single-Dose Option as a Reference Standard for Brain Tumors.

DSC-MR imaging using preload, intermediate (60°) flip angle and postprocessing leakage correction has gained traction as a standard methodology. Simulations suggest that DSC-MR imaging with flip angle = 30° and no preload yields relative CBV practically equivalent to the reference standard. This study tested this hypothesis in vivo. Eighty-four patients with brain lesions were enrolled in this 3-institution study. Forty-three patients satisfied the inclusion criteria. DSC-MR imaging (3T, single-dose gadobutrol, gradient recalled-echo-EPI, TE = 20-35 ms, TR = 1.2-1.63 seconds) was performed twice for each patient, with flip angle = 30°-35° and no preload (P-), which provided preload (P+) for the subsequent intermediate flip angle = 60°. Normalized relative CBV and standardized relative CBV maps were generated, including postprocessing with contrast agent leakage correction (C+) and without (C-) contrast agent leakage correction. Contrast-enhancing lesion volume, mean relative CBV, and contrast-to-noise ratio obtained with 30°/P-/C-, 30°/P-/C+, and 60°/P+/C- were compared with 60°/P+/C+ using the Lin concordance correlation coefficient and Bland-Altman analysis. Equivalence between the 30°/P-/C+ and 60°/P+/C+ protocols and the temporal SNR for the 30°/P- and 60°/P+ DSC-MR imaging data was also determined. Compared with 60°/P+/C+, 30°/P-/C+ had closest mean standardized relative CBV (P = .61), highest Lin concordance correlation coefficient (0.96), and lowest Bland-Altman bias (μ = 1.89), compared with 30°/P-/C- (P = .02, Lin concordance correlation coefficient = 0.59, μ = 14.6) and 60°/P+/C- (P = .03, Lin concordance correlation coefficient = 0.88, μ = -10.1) with no statistical difference in contrast-to-noise ratios across protocols. The normalized relative CBV and standardized relative CBV were statistically equivalent at the 10% level using either the 30°/P-/C+ or 60°/P+/C+ protocols. Temporal SNR was not significantly different for 30°/P- and 60°/P+ (P = .06). Tumor relative CBV derived from low-flip angle, no-preload DSC-MR imaging with leakage correction is an attractive single-dose alternative to the higher dose reference standard.

A standardised frankincense extract reduces disease activity in relapsing-remitting multiple sclerosis (the SABA phase IIa trial)

ObjectiveTo investigate whether oral administration of a standardised frankincense extract (SFE) is safe and reduces disease activity in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsWe performed an investigator-initiated, bicentric phase IIa,...

Relapse May Serve as a Mediator Variable in Longitudinal Outcomes in Multiple Sclerosis.

Contrast-enhancing lesions (CEL) on magnetic resonance imaging (MRI) are believed to represent inflammatory disease activity in multiple sclerosis (MS), but their relationship to subsequent long-term disability and progression is unclear, particularly at longer time periods such as 8-10 years. Between 1989 and 1994, 111 MS patients were seen at the National Institutes of Health for clinical evaluations and 3 monthly contrast-enhanced MRI scans. Of these, 94 patients were re-evaluated a mean of 8 years later (range 6.1-10.5 years) with a single MRI scan and clinical evaluation. CEL number and volume were determined at baseline and follow-up. The number of relapses was ascertained over the follow-up period and annualized relapse rates were calculated. Other MRI parameters, such as T2 hyperintensity volume, T1 volume, and brain parenchymal fraction, were also calculated. While there was no direct correlation between CEL number or volume at baseline and disability status at follow-up, CEL measures at baseline did correlate with number of relapses observed in the subsequent years, and the number of relapses in turn correlated with subsequent disability as well as transition to progressive MS. While number and volume of CEL at baseline do not directly correlate with disability in the longer term in MS, our data suggest that 1 route to disability involves relapses as a mediator variable in the causal sequence of MS progression from CEL to disability. Further studies using relapse as a mediator variable in a larger data set may be warranted.

High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study.

The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival.

Environmental Factors Associated with Disease Progression after the First Demyelinating Event: Results from the Multi-Center SET Study

ObjectivesTo investigate the associations of environmental MS risk factors with clinical and MRI measures of progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event.MethodsWe analyzed 211 CIS patients (age: 28.9±7.8 years) enrolled in the SET study, a multi-center study of high-risk CIS patients. Pre-treatment samples were analyzed for IgG antibodies against cytomegalovirus (anti-CMV), Epstein Barr virus (EBV) early nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA), early antigen-diffuse (EA-D), 25 hydroxy-vitamin D3 and cotinine levels and HLA DRB1*1501 status. The inclusion criteria required evaluation within 4 months of the initial demyelinating event, 2 or more brain MRI lesions and the presence of two or more oligoclonal bands in cerebrospinal fluid. All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months.ResultsThe time to first relapse decreased and the number of relapses increased with anti-CMV IgG positivity. Smoking was associated with increased number and volume of contrast-enhancing lesions (CEL) during the 2-year period. The cumulative number of CEL and T2 lesions during the 2-year period was greater for individuals in the highest quartile of anti-EBV VCA IgG antibodies. The percent loss of brain volume was increased for those in the highest quartile of with anti-EBV VCA IgG antibodies.ConclusionsRelapses in CIS patients were associated with CMV positivity whereas anti-EBV VCA positivity was associated with progression on MRI measures, including accumulation of CEL and T2 lesions and development of brain atrophy.

Serum lipid profiles are associated with disability and MRI outcomes in multiple sclerosis

BackgroundThe breakdown of the blood-brain-barrier vascular endothelium is critical for entry of immune cells into the MS brain. Vascular co-morbidities are associated with increased risk of progression. Dyslipidemia, elevated LDL and reduced HDL may increase progression by activating inflammatory processes at the vascular endothelium.ObjectiveTo assess the associations of serum lipid profile variables (triglycerides, high and low density lipoproteins (HDL, LDL) and total cholesterol) with disability and MRI measures in multiple sclerosis (MS).MethodsThis study included 492 MS patients (age: 47.1 ± 10.8 years; disease duration: 12.8 ± 10.1 years) with baseline and follow-up Expanded Disability Status Score (EDSS) assessments after a mean period of 2.2 ± 1.0 years. The associations of baseline lipid profile variables with disability changes were assessed. Quantitative MRI findings at baseline were available for 210 patients.ResultsEDSS worsening was associated with higher baseline LDL (p = 0.006) and total cholesterol (p = 0.001, 0.008) levels, with trends for higher triglyceride (p = 0.025); HDL was not associated. A similar pattern was found for MSSS worsening. Higher HDL levels (p < 0.001) were associated with lower contrast-enhancing lesion volume. Higher total cholesterol was associated with a trend for lower brain parenchymal fraction (p = 0.033).ConclusionsSerum lipid profile has modest effects on disease progression in MS. Worsening disability is associated with higher levels of LDL, total cholesterol and triglycerides. Higher HDL is associated with lower levels of acute inflammatory activity.

The effect of interferon beta-1b on size of short-lived enhancing lesions in patients with multiple sclerosis

Background: Contrast enhancing lesions (CELs) in MRI represent inflammatory events in multiple sclerosis (MS). IFN-β-1b decreases the formation of CELs. However, the ability of IFN-β-1b to reduce the size of CELs arising during therapy has not been extensively investigated. Methods: Thirty patients with relapsing-remitting (RR) MS were followed for a 3-month pre-therapy phase then for a 6-month therapy phase during which treatment with IFN-β-1b at a dosage of 250 μg subcutaneously injected every other day was employed. Each patient underwent monthly clinical and MRI examinations. For all patients, CELs were identified on postcontrast T1-weighted MRIs. CEL number, size, and volume were computed using Medx software. Results: The average number and total lesion volume of CELs visible during the therapy phase were significantly lower than the number and total lesion volume of CELs observed in the pre-therapy phase. However, there was no significant reduction between pre-therapy and therapy phases in the mean size of individual lesions arising during the respective phases. Conclusions: Since size of CELs has been related to severity of tissue damage, the lack of size decrease during therapy suggested a limited therapeutic effect of IFN-β-1b if a blood–brain barrier breakdown has occurred.

An exploratory study on interferon beta dose effect in reducing size of enhancing lesions in multiple sclerosis

Sixty-two patients with multiple sclerosis (MS) were imaged monthly over a six-month (ie, seven monthly magnetic resonance images [MRI]) natural history period (NHP). Thereafter, patients were randomized to receive 11 or 33 μg of subcutaneously injected interferon beta 1a (IFNp-1 a) with imaging monthly for nine months and at months 12, 18 and 24 of therapy phase (TP). In the present exploratory post hoc analysis, the authors evaluated IFNβ-1a dose effect on reducing the size of contrast-enhancing lesions (CELs). MRIs performed at months 0, 3 and 6 of NHP and at months 3, 6, 9, 18 and 24 of TP were analysed. While a significant reduction in mean number of CELs was observed in both treatment groups of patients, the mean total volume and size of CELs was reduced only in patients undergoing therapy with 33 μg of IFNβ-1a. The latter suggests a significant dose effect exerted by IFNβ-1a in the evolution of CELs' dimensions during therapy. Multiple Sclerosis 2007; 13: 343-347. http://msj.sagepub.com

Analysis of the spatial characteristics of metabolic abnormalities in newly diagnosed glioma patients.

To evaluate the role of 3D MR spectroscopic imaging (MRSI) as a tool for characterizing heterogeneity within a lesion in glioma patients. Forty-nine patients with newly diagnosed glioma were studied with 3D water-suppressed proton (1-H) MRSI. Signal intensities from choline (Cho), creatine (Cr), N-acytel aspartate (NAA), and lactate/lipid (LL) were estimated from the spectra. Regions of interest (ROIs) corresponding to the metabolic abnormalities were defined and compared with the anatomic lesions. This study showed that the tumor burden measured with either the volumes of the metabolic abnormalities or the metabolic levels in the most abnormal voxels was correlated with the degree of malignancy of the tumor. The volumes of elevated Cho and decreased NAA were useful for distinguishing low-grade from high-grade lesions. The volume of abnormal LL was correlated with the existence of necrosis and with the volume of contrast-enhancing lesions in high-grade lesions. The differences in the volume of abnormal LL were also statistically significant between patients in each grade. These 3D-MRSI data provide important additional information to conventional MRI for evaluating and characterizing gliomas.

Transient enlargement of contrast uptake on MRI after linear accelerator (linac) stereotactic radiosurgery for brain metastases

Purpose/Objective: With the increasing number of patients successfully treated with stereotactic radiosurgery for brain metastases, decision making after therapy based on follow-up imaging findings becomes more and more important. Magnetic resonance imaging (MRI) is the most sensitive means for follow-up studies. The objective of this study was to investigate the treatment outcome of our radiosurgery program and to describe the response of brain metastases to contrast-enhanced MRI after linear accelerator (linac) stereotactic radiosurgery and identify factors to distinguish among local control and local failure. Methods and Materials: Using serial MRI, we followed the course of 87 brain metastases in 48 consecutive patients treated between September 1996 and November 1997 with linac-based radiosurgery with 15-MV photons. Treatment planning was performed on an MR data cube. For spherical metastases, radiosurgery was delivered using a 9 noncoplanar arc technique with circular-shaped collimators. For irregularly shaped targets, radiosurgery was delivered using a manually driven multi-leaf collimator with a leaf width of 1.5 mm projected to the isocenter. Median radiosurgery dose was 20 Gy prescribed to the 80% isodose. Together with whole brain radiotherapy (20 × 2 Gy, 5/w), a median radiosurgical dose of 15 Gy was delivered. Median follow-up was 8 (range 2–36) months. Factors influencing local control and survival rates were analyzed with respect to MRI response, and Kaplan-Meier curves were calculated. Results: Actuarial local tumor control was 91% at one and two years. Patient survival at one and two years was 30% and 18%. Median survival was 9 months. During follow-up in 70 (81%) of the 87 treated metastases, the contrast-enhancing volumes on T1W images were stable or disappeared partly or completely. A transient enlargement of contrast-enhancing volumes was observed in 11 (12%) of the 87 lesions treated, while a progressive enlargement due to local treatment failure was observed in 6 (7%) of the 87 treated metastases. Younger age, early contrast onset after radiosurgery, and previous chemotherapy were associated with this transient enlargement of contrast-enhancing lesion volume. Conclusions: Linac-based radiosurgery is an effective, noninvasive, and safe treatment option for patients with brain metastases. A marked enlargement of the contrast-enhancing volume on T 1-weighted MR images after radiosurgery is a sensitive predictor for, but not equivalent with, local failure. In as many as two-thirds of the cases with contrast enlargement in MRI follow-up, the contrast enlargement is transient with no need for further treatment. While some MRI findings are more likely if transient enlargement is present, a clear decision cannot be made based on MRI, and ultimately the clinical status dictates further action.