Prehypertensive blood pressures and regional cerebral blood flow independently relate to cognitive performance in midlife

Background High blood pressure is thought to contribute to dementia in late life, but our understanding of the relationship between individual differences in blood pressure ( BP ) and cognitive functioning is incomplete. In this study, cognitive performance in nonhypertensive midlife adults was examined as a function of resting BP and regional cerebral blood flow ( rCBF ) responses during cognitive testing. We hypothesized that BP would be negatively related to cognitive performance and that cognitive performance would also be related to rCBF responses within areas related to BP control. We explored whether deficits related to systolic BP might be explained by rCBF responses to mental challenge. Methods and Results Healthy midlife participants (n=227) received neuropsychological testing and performed cognitive tasks in a magnetic resonance imaging scanner. A pseudocontinuous arterial spin labeling sequence assessed rCBF in brain areas related to BP in prior studies. Systolic BP was negatively related to 4 of 5 neuropsychological factors (standardized β&gt;0.13): memory, working memory, executive function, and mental efficiency. The rCBF in 2 brain regions of interest was similarly related to memory, executive function, and working memory (standardized β&gt;0.17); however, rCBF responses did not explain the relationship between resting systolic BP and cognitive performance. Conclusions Relationships at midlife between prehypertensive levels of systolic BP and both cognitive and brain function were modest but suggested the possible value of midlife intervention. </jats:sec

Technical note: Institutional solution of clinical cine MRI for tumor motion evaluation in radiotherapy

PURPOSE: Since 4D-MRI is inadequate to capture dynamic respiratory variations, real-time cinematographic (cine) MRI is actively used in MR-guided radiotherapy (MRgRT) for tumor motion evaluation, delineation, and tracking. However, most radiotherapy imaging platforms do not support the format of cine MRI from clinical MRI systems. This study developed an institutional solution of clinical cine MRI for tumor motion evaluation in radiotherapy applications. METHODS: Cine MRI manipulation software (called Cine Viewer) was developed within a commercial Treatment Planning System (TPS). It consists of (1) single/orthogonal viewers, (2) display controllers, (3) measurement grids/markers, and (4) manual contouring tools. RESULTS: The institutional solution of clinical cine MRI incorporated with radiotherapy application was assessed through case presentations (liver cancer). Cine Viewer loaded cine MRIs from 1.5T Philips Ingenia MRI, handling MRI DICOM format. The measurement grids and markers were used to quantify the displacement of anatomical structures in addition to the tumor. The contouring tool was utilized to localize the tumor and surrogates on the designated frame. The stacks of the contours were exhibited to present the ranges of tumor and surrogate motions. For example, the stacks of the tumor contours from case-1 were used to determine the ranges of tumor motions (∼8.17 mm on the x-direction [AP-direction] and ∼14 mm on the y-direction [SI-direction]). In addition, the patterns of the displacement of the contours over frames were analyzed and reported using in-house software. In the case-1 review, the tumor was displaced from +146.0 mm on the x-direction and +125.0 mm on the y-direction from the ROI of the abdominal surface. CONCLUSION: We demonstrated the institutional solution of clinical cine MRI in radiotherapy. The proposed tools can streamline the utilization of cine MRI for tumor motion evaluation using Eclipse for treatment planning

Evaluation of diffusion-weighted MRI and geometric distortion on a 0.35T MR-LINAC at multiple gantry angles

Diffusion-weighted imaging (DWI) provides a valuable diagnostic tool for tumor evaluation. Yet, it is difficult to acquire daily MRI data sets in the traditional radiotherapy clinical setting due to patient burden and limited resources. However, integrated MRI radiotherapy treatment systems facilitate daily functional MRI acquisitions like DWI during treatment exams. Before ADC values from MR-RT systems can be used clinically their reproducibility and accuracy must be quantified. This study used a NIST traceable DWI phantom to verify ADC values acquired on a 0.35 T MR-LINAC system at multiple gantry angles. A diffusion-weighted echo planar imaging sequence was used for all image acquisitions, with b-values of 0, 500, 900, 2000 s/m

Targeted delivery of bleomycin to the brain using photo-chemical internalization of Clostridium perfringens epsilon prototoxin

Cells infiltrating into normal brain from malignant brain tumors are protected by the blood brain barrier (BBB) which prevents the delivery and limits the effects of anti-tumor agents. We have evaluated the ability of photochemical internalization (PCI) to limit the effects of an agent known to broadly open the BBB to a target region of the brain. The PCI-based relocation and activation of macromolecules into the cell cytosol has the advantage of minimal side effects since the effect is localized to the area exposed to light, allowing the access of chemotherapeutic agents only to these regions. Non tumor bearing inbred Fisher rats were treated with photosesitizer, and a nontoxic intraperitoneal dose of Clostridium perfringens epsilon prototoxin (ETXp) followed by light exposure. Post-contrast T1 MRI scans were used to monitor the degree BBB disruption. F98 tumor cells were implanted into the brains of other animals that were subsequently treated 24 h later with ETXp-PCI BBB opening followed by the i.p. administration of bleomycin (BLM). PCI delivery of ETXp at low fluence levels demonstrated significant MRI enhancement. No effect on the BBB was observed if photosesitizer and light was given in the absence ETXp. The survival of animals implanted with F98 tumor cells was significantly extended following ETXp-PCI BBB opening and BLM therapy compared to controls. PCI delivered ETXp was effective in opening the BBB in a limited region of the brain. ETXp-PCI mediated BBB opening clearly increased the efficacy of BLM therapy

Feasibility of surface-guidance combined with CBCT for intra-fractional breath-hold motion management during Ethos RT

PURPOSE: High-quality CBCT and AI-enhanced adaptive planning techniques allow CBCT-guided stereotactic adaptive radiotherapy (CT-STAR) to account for inter-fractional anatomic changes. Studies of intra-fractional respiratory motion management with a surface imaging solution for CT-STAR have not been fully conducted. We investigated intra-fractional motion management in breath-hold Ethos-based CT-STAR and CT-SBRT (stereotactic body non-adaptive radiotherapy) using optical surface imaging combined with onboard CBCTs. METHODS: Ten cancer patients with mobile lower lung or upper abdominal malignancies participated in an IRB-approved clinical trial (Phase I) of optical surface image-guided Ethos CT-STAR/SBRT. In the clinical trial, a pre-configured gating window (± 2 mm in AP direction) on optical surface imaging was used for manually triggering intra-fractional CBCT acquisition and treatment beam irradiation during breath-hold (seven patients for the end of exhalation and three patients for the end of inhalation). Two inter-fractional CBCTs at the ends of exhalation and inhalation in each fraction were acquired to verify the primary direction and range of the tumor/imaging-surrogate (donut-shaped fiducial) motion. Intra-fractional CBCTs were used to quantify the residual motion of the tumor/imaging-surrogate within the pre-configured breath-hold window in the AP direction. Fifty fractions of Ethos RT were delivered under surface image-guidance: Thirty-two fractions with CT-STAR (adaptive RT) and 18 fractions with CT-SBRT (non-adaptive RT). The residual motion of the tumor was quantified by determining variations in the tumor centroid position. The dosimetric impact on target coverage was calculated based on the residual motion. RESULTS: We used 46 fractions for the analysis of intra-fractional residual motion and 43 fractions for the inter-fractional motion analysis due to study constraints. Using the image registration method, 43 pairs of inter-fractional CBCTs and 100 intra-fractional CBCTs attached to dose maps were analyzed. In the motion range study (image registration) from the inter-fractional CBCTs, the primary motion (mean ± std) was 16.6 ± 9.2 mm in the SI direction (magnitude: 26.4 ± 11.3 mm) for the tumors and 15.5 ± 7.3 mm in the AP direction (magnitude: 20.4 ± 7.0 mm) for the imaging-surrogate, respectively. The residual motion of the tumor (image registration) from intra-fractional breath-hold CBCTs was 2.2 ± 2.0 mm for SI, 1.4 ± 1.4 mm for RL, and 1.3 ± 1.3 mm for AP directions (magnitude: 3.5 ± 2.1 mm). The ratio of the actual dose coverage to 99%, 90%, and 50% of the target volume decreased by 0.95 ± 0.11, 0.96 ± 0.10, 0.99 ± 0.05, respectively. The mean percentage of the target volume covered by the prescribed dose decreased by 2.8 ± 4.4%. CONCLUSION: We demonstrated the intra-fractional motion-managed treatment strategy in breath-hold Ethos CT-STAR/SBRT using optical surface imaging and CBCT. While the controlled residual tumor motion measured at 3.5 mm exceeded the predetermined setup value of 2 mm, it is important to note that this motion still fell within the clinically acceptable range defined by the PTV margin of 5 mm. Nonetheless, additional caution is needed with intra-fractional motion management in breath-hold Ethos CT-STAR/SBRT using optical surface imaging and CBCT