23 research outputs found
Functional Near-Infrared Spectroscopy to Probe State- and Trait-Like Conditions in Chronic Tinnitus: A Proof-of-Principle Study
Objective. Several neuroscience tools showed the involvement of auditory cortex in chronic tinnitus. In this proof-of-principle study we probed the capability of functional near-infrared spectroscopy (fNIRS) for the measurement of brain oxygenation in auditory cortex in dependence from chronic tinnitus and from intervention with transcranial magnetic stimulation. Methods. Twenty-three patients received continuous theta burst stimulation over the left primary auditory cortex in a randomized sham-controlled neuronavigated trial (verum = 12; placebo = 11). Before and after treatment, sound-evoked brain oxygenation in temporal areas was measured with fNIRS. Brain oxygenation was measured once in healthy controls (n = 12). Results. Sound-evoked activity in right temporal areas was increased in the patients in contrast to healthy controls. Left-sided temporal activity under the stimulated area changed over the course of the trial; high baseline oxygenation was reduced and vice versa. Conclusions. By demonstrating that rTMS interacts with auditory evoked brain activity, our results confirm earlier electrophysiological findings and indicate the sensitivity of fNIRS for detecting rTMS induced changes in brain activity. Moreover, our findings of trait-and state-related oxygenation changes indicate the potential of fNIRS for the investigation of tinnitus pathophysiology and treatment response
Bevacizumab and carboplatin increase survival and asymptomatic tumor volume in a glioma model
To evaluate efficacy and MRI findings after intravenous bevacizumab and/or carboplatin in a human glioma animal model, we randomized male nude rats with intracerebral UW28 human glioma xenografts to four groups: (1) controls (n = 9), (2) bevacizumab 10 mg/kg (n = 6), (3) carboplatin 200 mg/m2 (n = 6), and (4) bevacizumab + carboplatin (n = 6). MRI was performed on the day of treatment (day 7–10) and 1 week later, and rats were followed for survival. Dynamic MRI was done in three controls and three rats treated with bevacizumab with or without carboplatin before and 24 h after treatment. Median overall survival (OS) was as follows: group 1, 16 days; group 2, 23 days; group 3, 22 days; group 4, 36 days. OS was significantly longer in group 4 than in group 1 (p = 0.0011), group 2 (p = 0.0014), and group 3 (p = 0.0015), and rats had significantly larger tumors. No objective tumor responses were observed on MR images at 1 week after treatment; however, after bevacizumab, dynamic MRI showed reduced gadolinium enhancement intensity and increased time to peak, consistent with decreased vascular permeability. Carboplatin + bevacizumab is effective and superior over bevacizumab or carboplatin monotherapy in this animal model. Increased survival concomitant with increased asymptomatic tumor volume is suggestive that vascular targeting with reduced peritumoral edema and mass effect contributes to the efficacy of bevacizumab. The promising survival data warrant future clinical trials using bevacizumab + carboplatin
Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models1
Abstract The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX) on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally) 24 hours before human ovarian carcinoma (SKOV3), small cell lung carcinoma (LX-1 SCLC), and glioma (UW28, U87MG, and U251) tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0%) of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive) infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues
Neuronavigated left temporal continuous theta burst stimulation in chronic tinnitus
Purpose: Clinical effects of repetitive transcranial magnetic stimulation (rTMS) in chronic tinnitus are moderate. More precise coil localisation strategies, innovative stimulation protocols, and identification of predictors for treatment response were proposed as promising attempts to enhance treatment efficacy. In this pilot study we investigated neuronavigated continuous theta burst TMS (cTBS). Methods: Twenty-three patients received neuronavigated cTBS over the left primary auditory cortex in a randomized sham-controlled trial (verum = 12; sham = 11). Treatment response was evaluated with tinnitus questionnaires and numeric rating scales. Immediate change in numeric rating scales during the first session was used as predictor for treatment response. Results: Tinnitus was significantly reduced after treatment, but there were no superior effects between verum vs. sham treatment. Immediate change in the first treatment session predicted the response to treatment only in the verum group. Conclusions: In our study, verum cTBS was not superior to sham which highlights the persistent need for improving non-invasive brain stimulation techniques for the treatment of tinnitus. Future research should focus on the transfer of positive single session effects to daily treatment trials
Long-Term Outcomes of Intra-Arterial Chemotherapy for Progressive or Unresectable Pilocytic Astrocytomas: Case Studies.
BACKGROUND: Progressive and/or unresectable pilocytic astrocytomas (PAs) carry a poor prognosis compared to typical PA. Early radiotherapy (RT) may have severe long-term neurocognitive side effects in this patient population. Intra-arterial (IA) chemotherapy is a viable alternative or addition to intravenous (IV) chemotherapy, which may be beneficial in avoidance of early RT.
OBJECTIVE: To evaluate the safety and efficacy of IA chemotherapy in this subset of patients.
METHODS: This is a retrospective review of medical records of PA patients who are treated with IA chemotherapy at Oregon Health & Science University from 1997 until 2019. Response to treatment was categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Progression free survival (PFS) and overall survival (OS) are also reported.
RESULTS: Twelve patients were identified. All patients experienced progression prior to initiation of IA chemotherapy. The most common grade 3 or 4 toxicities related to chemotherapy were thrombocytopenia (66%), neutropenia (66%), leukopenia (50%), anemia (33%), and lymphopenia (16%). Responses achieved were CR in 1, PR in 3, SD in 7, and PD in 1. Median PFS and median OS were 16.5 and 83.5 mo, respectively. A total of 112 procedures (IA injections) were performed and 250 arteries were catheterized. There were 3 minor and no major complications attributable to procedures.
CONCLUSION: This study demonstrates that IA chemotherapy can be safely used in patients with unresectable or progressive PA
Efficacy and MRI of rituximab and methotrexate treatment in a nude rat model of CNS lymphoma
To determine the efficacy of methotrexate and/or rituximab in a CNS lymphoma model and to evaluate MRI modalities for monitoring efficacy, we inoculated female athymic nude rats (rnu/rnu) intracerebrally with human MC116 B-lymphoma cells. Between days 16 and 26, rats were randomized to receive intravenous (IV) treatment with (1) saline (controls, n = 15), (2) methotrexate 1,000 mg/m2 (n = 6), (3) rituximab 375 mg/m2 (n = 6), or (4) rituximab plus methotrexate (n = 6). T2/fluid-attenuated inversion recovery (FLAIR) and gadolinium contrast-enhanced T1 MRI sequences were performed prior to and 1 week after treatment. IV rituximab gave an objective tumor response in four of six animals (>50% reduction in tumor volume comparing pre- and posttreatment T2/FLAIR MRI) and resulted in stable disease (50%–125% of baseline) in another animal. The percent change in tumor volume on T2/FLAIR images was significantly different in the control versus rituximab group (p = 0.0051). IV methotrexate slowed tumor growth, compared to controls, but only one of six animals had an objective response. In untreated controls, tumor histological volumes correlated well with T2/FLAIR or contrast-enhanced T1 images (r = 0.877). In the treatment groups, T2/FLAIR correlation was good, but the gadolinium-enhanced T1 MRI was not significantly correlated with histology (r = 0.19). The MC116 CNS lymphoma model seems valuable for preclinical testing of efficacy and toxicity of treatment regimens. IV rituximab was highly effective, but methotrexate was only minimally effective. T2/FLAIR was superior to contrast-enhanced T1 for monitoring efficacy
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Pseudoprogression of Glioblastoma after Chemo- and Radiation Therapy: Diagnosis by Using Dynamic Susceptibilityweighted Contrast-enhanced Perfusion MR Imaging with Ferumoxytol versus Gadoteridol and Correlation with Survival
This file has been removed from the repository due to a DMCA Takedown Notice.- - - -[Purpose]
To compare gadoteridol and ferumoxytol for measurement of relative cerebral blood volume (rCBV) in patients with glioblastoma multiforme (GBM) who showed progressive disease at conventional magnetic resonance (MR) imaging after chemo- and radiation therapy (hereafter, chemoradiotherapy) and to correlate rCBV with survival.
[Materials and Methods]
Informed consent was obtained from all participants before enrollment in one of four institutional review board–approved protocols. Contrast agent leakage maps and rCBV were derived from perfusion MR imaging with gadoteridol and ferumoxytol in 19 patients with apparently progressive GBM on conventional MR images after chemoradiotherapy. Patients were classified as having high rCBV (>1.75), indicating tumor, and low rCBV (≤1.75), indicating pseudoprogression, for each contrast agent separately, and with or without contrast agent leakage correction for imaging with gadoteridol. Statistical analysis was performed by using Kaplan-Meier survival plots with the log-rank test and Cox proportional hazards models.
[Results]
With ferumoxytol, rCBV was low in nine (47%) patients, with median overall survival (mOS) of 591 days, and high rCBV in 10 (53%) patients, with mOS of 163 days. A hazard ratio of 0.098 (P = .004) indicated significantly improved survival. With gadoteridol, rCBV was low in 14 (74%) patients, with mOS of 474 days, and high in five (26%), with mOS of 156 days and a nonsignificant hazard ratio of 0.339 (P = .093). Five patients with mismatched high rCBV with ferumoxytol and low rCBV with gadoteridol had an mOS of 171 days. When leakage correction was applied, rCBV with gadoteridol was significantly associated with survival (hazard ratio, 0.12; P = .003).
[Conclusion]
Ferumoxytol as a blood pool agent facilitates differentiation between tumor progression and pseudoprogression, appears to be a good prognostic biomarker, and unlike gadoteridol, does not require contrast agent leakage correction.Keywords: Cerebral blood volume, Predict, Pseudo progression, Tumor progression, Brain tumors, High grade gliomas, Concomitant radiochemotherapy, Temozolomide, Central nervous system, Malignant gliomaKeywords: Cerebral blood volume, Predict, Pseudo progression, Tumor progression, Brain tumors, High grade gliomas, Concomitant radiochemotherapy, Temozolomide, Central nervous system, Malignant gliom