Purpose: To evaluate the reproducibility and gender differences in cerebrovascular reactivity (CVR) measurements obtained using the blood-oxygen level dependent (BOLD) response to controlled changes in end-tidal partial pressure of carbon dioxide (PETCO 2 ). Materials and Methods:We obtained ethical approval to image 19 healthy volunteers (10 men, 9 women) on a 1.5 Tesla (T) MRI scanner twice on two separate days using identical procedures. CVR images were generated by collecting BOLD MRI data during controlled changes in PETCO 2 induced by a sequential gas delivery system.Results: Using the intraclass correlation coefficient (ICC), we demonstrated excellent within-day CVR measures in gray matter (GM) (ICC ¼ 0.92) and white matter (WM) (ICC ¼ 0.88) regions, excellent between-day reproducibility in GM (ICC ¼ 0.81), and good between-day reproducibility in the WM (ICC ¼ 0.66). CVR values between men and women were significantly different in the GM and WM. Men exhibited a 22 6 2% greater CVR in GM and a 17 6 2% greater CVR in WM compared with females.Conclusion: Our results demonstrate the reliability of BOLD MRI CVR measurements obtained using a controlled cerebrovascular challenge. Using this technique, we also revealed significantly increased BOLD response to CO 2 in males compared with females.

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IMPORTANCERising cancer incidence combined with improvements in systemic and local therapies extending life expectancy are translating into more patients with spinal metastases. This makes the multidisciplinary management of spinal metastases and development of new therapies increasingly important. Spinal metastases may cause significant pain and reduced quality of life and lead to permanent neurological disability if compression of the spinal cord and/or nerve root occurs. Until recently, treatments for spinal metastases were not optimal and provided temporary local control and pain relief. Spinal stereotactic ablative radiotherapy (SABR) is an effective approach associated with an improved therapeutic ratio, with evolving clinical application.OBJECTIVE To review the literature of spinal SABR for spinal metastases, discuss a multidisciplinary approach to appropriate patient selection and technical considerations, and summarize current efforts to combine spinal SABR with systemic therapies. EVIDENCE REVIEWThe MEDLINE database was searched to identify articles reporting on spinal SABR to September 30, 2018. Articles including clinical trials, prospective and retrospective studies, systematic reviews, and consensus recommendations were selected for relevance to multidisciplinary management of spinal metastases.RESULTS Fifty-nine unique publications with 5655 patients who underwent SABR for spinal metastases were included. Four comprehensive frameworks for patient selection were discussed. Spinal SABR was associated with 1-year local control rates of approximately 80% to 90% in the de novo setting, greater than 80% in the postoperative setting, and greater than 65% in the reirradiation setting. The most commonly discussed adverse effect was development of a vertebral compression fracture with variable rates, most commonly reported as approximately 10% to 15%. High-level data on the combination of SABR with modern therapies are still lacking. At present, 19 clinical trials are ongoing, mainly focusing on combined modality therapies, radiotherapy prescription dose, and oligometastic disease.CONCLUSIONS AND RELEVANCE These findings suggest that spinal SABR may be an effective treatment option for well-selected patients with spinal metastases, achieving high rates of local tumor control with moderate rates of adverse effects. Optimal management should include review by a multidisciplinary care team.

Magnetic resonance imaging (MRI) relaxation times provide indirect estimates of tissue O(2) for monitoring tumour oxygenation. This study provides insight into mechanisms underlying longitudinal (R(1) = 1/T(1)) and transverse effective (R(2)* = 1/T(2)*) relaxation rate changes during inhalation of 100% O(2) and 3%, 6% and 9% CO(2) (balanced O(2)) in a rabbit tumour model. Quantitative R(1), R(2)*, and dynamic contrast-enhanced (DCE) imaging was performed in six rabbits 12-23 days following implantation of VX2 carcinoma cells in the quadricep muscle. Invasive measurements of tissue partial pressure of O(2) (pO(2)) and perfusion were also performed, which revealed elevated pO(2) levels in all tumour regions for all hyperoxic gases compared to baseline (air) and reduced perfusion for carbogen. During 100% O(2) breathing, an R(1) increase and R(2)* decrease consistent with elevated pO(2) were observed within tumours. DCE-derived blood flow was weakly correlated with R(1) changes from air to 100% O(2). Further addition of CO(2) (carbogen) did not introduce considerable changes in MR relaxation rates, but a trend towards higher R(1) relative to breathing 100% O(2) was observed, while R(2)* changes were inconsistent. This observation supports the predominance of dissolved O(2) on R(1) sensitivity and demonstrates the value of R(1) over R(2)* for tissue oxygenation measures.

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