A Study of Dose Painting Radiotherapy Guided by Three-Dimensional Arterial Spin labeling Perfusion Magnetic Resonance Imaging for Non-Enhancing Low-Grade Gliomas

Background: The purpose of this study was to investigate the feasibility and dosimetric characteristics of dose painting for non-enhancing low-grade gliomas (NE-LGGs) guided by three-dimensional arterial spin labeling (3D-ASL) perfusion magnetic resonance imaging.Methods: Eighteen patients with NE-LGGs were enrolled. 3D-ASL, T2 fluid attenuated inversion recovery (T2 FLAIR) and contrast-enhanced T1-weight magnetic resonance images were obtained. The gross tumor volume (GTV) was delineated on the T2 FLAIR. The hyper-perfusion region of the GTV (GTV-ASL) was determined by 3D-ASL, and the GTV-SUB was obtained by subtracting the GTV-ASL from the GTV. The planning target volume (PTV), PTV-ASL and PTV-SUB were developed by expanding the external margins of the GTV, GTV-ASL and GTV-SUB, respectively. Three plans were established for each patient: in plan 1, the traditional homogeneous prescription dose to the PTV was 45-60 Gy; in plan 2 and plan 3, the dose to the PTV-ASL increased by 10-20% based on plan 1, without the maximum dose constraint to the PTV-ASL in plan 3. The dosimetric differences among the three plans were compared.Results: Compared with plan 1, the dose to 2% (D2%), 98% (D98%) and 50% (Dmean) of PTV-ASL volumes increased by 14.67%, 16.17% and 14.31% in plan 2 and 19.84%, 15.52% and 14.27% in plan 3, respectively (P < 0.05); the D2% of the PTV, PTV-SUB increased by 11.89% and 8.34% in plan 2, 15.89% and 8.49% in plan 3, respectively (P< 0.05). The PTV coverages were comparable among the three plans (P > 0.05). In Plan 2 and plan 3, the conformity indexs decreased by 18.60% and 12.79%; while the homogeneity indexs increased by 1.43 and 2 times (P<0.05). Compared with plan 1, the D0.1cc of brain stem and Dmax of optic chiasma slightly increased in plan 2 and plan 3, but the absolute doses met the dose constraint. The other organs at risk were similar among the three plans (P > 0.05).Conclusions: The sub-volume with hyper-perfusion for NE-LGG radiotherapy can be segmented based on the perfusion difference guided by 3D-ASL. And the radiation dose to the hyper-perfusion area increased safely by 10-20% through dose painting.

Perfusion Defects and Collateral Flow Patterns in Acute Small Subcortical Infarction: a 4D Dynamic MRI Study

The hemodynamic changes of acute small subcortical infarction (SSI) are not well understood. We evaluate the hemodynamic changes and collaterals in acute SSI using perfusion magnetic resonance imaging (MRI). A total of 103 patients with acute SSI in penetrating artery territories were recruited and underwent MRI within 24 h of stroke onset. Using 4D dynamic perfusion MRI, they were divided into three patterns: 25 (24%) with normal perfusion, 31 (30%) with compensated perfusion, and 47 (46%) with hypoperfusion. The development of anterograde or retrograde collaterals was also evaluated. Patients with hypoperfusion pattern had the highest rate of early neurological deterioration (32%, p = 0.007), the largest initial and final infarction volumes (p < 0.001 and p = 0.029), the lowest relative cerebral blood flow (0.63, p < 0.001), and the lowest rate of anterograde and retrograde collaterals (19%, p < 0.001; 66%, p = 0.002). The anterograde collaterals were associated with higher relative cerebral blood volume (0.91 vs. 0.77; p = 0.024) and a higher rate of deep cerebral microbleeds (48 vs. 21%; p = 0.028), whereas retrograde collaterals were associated with higher systolic and diastolic blood pressure (p = 0.031 and 0.020), smaller initial infarction volume (0.81 vs. 1.34 ml, p = 0.031), and a higher rate of lobar cerebral microbleeds (30 vs. 0%; p = 0.013). Both anterograde and retrograde collaterals may play a critical role in maintaining cerebral perfusion and can have an impact on patient clinical outcomes. Further studies are warranted to verify these findings and to investigate effective treatments.

Cerebral Blood Flow Difference Between Acute and Chronic Tinnitus Perception: A Perfusion Functional Magnetic Resonance Imaging Study

Purpose: The central nervous mechanism of acute tinnitus is different from that of chronic tinnitus, which may be related to the difference of cerebral blood flow (CBF) perfusion in certain regions. To verify this conjecture, we used arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in this study to compare the CBF alterations of patients with acute and chronic tinnitus.Methods: The current study included patients with chronic tinnitus (n = 35), acute tinnitus (n = 30), and healthy controls (n = 40) who were age-, sex-, and education-matched. All participants underwent MRI scanning and then ASL images were obtained to measure CBF of the entire brain and analyze the differences between groups as well as the correlations with tinnitus characteristics.Results: The chronic tinnitus group showed increased z-CBF in the right superior temporal gyrus (STG) and superior frontal gyrus (SFG) when compared with the acute tinnitus patients. Further connectivity analysis found enhanced CBF connectivity between the right STG and fusiform gyrus (FG), the right SFG and left middle occipital gyrus (MOG), as well as the right parahippocampal gyrus (PHG). Moreover, in the chronic tinnitus group, the tinnitus handicap questionnaire (THQ) score was positively correlated with the normalized z-CBF of right STG (r = 0.440, p = 0.013).Conclusion: Our results confirmed that the CBF changes in some brain regions were different between acute and chronic tinnitus patients, which was correlated with certain tinnitus characteristics. This is of great value to further research on chronicity of tinnitus, and ASL has a promising application in the measurement of CBF.

Stress cardiac MRI for the evaluation of CCS patients in a real-world tertiary care center

Background The MR INFORM trial demonstrated that myocardial perfusion Magnetic Resonance Imaging (MRI) is non-inferior to Invasive Coronary Angiography (ICA) with measurement of Fractional Flow Reserve (FFR) in guiding the management of patients with stable coronary artery disease with respect to major adverse cardiac events, despite a reduced rate of revascularized patients. We sought to evaluate if a MRI-based strategy performed well also in patients with Chronic Coronary Syndrome (CCS) with intermediate coronary plaques observed by Coronary Computed Tomography Angiography (CCTA). Methods At our tertiary care center, patients with suspicion of CCS at intermediate risk first underwent CCTA. Subsequently, those showing intermediate coronary plaques underwent dipyridamole stress cardiac MRI. Revascularization was recommended for patients showing ischemia in at least two consecutive left ventricular segments or 6% of the myocardium. ICA and instantaneous FFR was performed in all of these patients, in order to confirm the indication for revascularization. The endpoint was a composite of death, non-fatal myocardial infarction, and target-vessel revascularization within 1 year. Results 55 patients at intermediate risk underwent CCTA. 15 patients with no or only minimal plaques (stenosis &lt;30%) and those with obstructive plaques (stenosis &gt;70%) were excluded. 40 patients showed intermediate plaques (30–70% stenosis): 102 plaques total were classified as: non calcified n=9 (9%), calcified n=48 (47%), and mixed n=45 (44%). These patients underwent stress MRI, on the basis of which n=12 (30%) patients met criteria to recommend revascularization, whereas n=28 (70%) did not. The indication for revascularization was confirmed by ICA plus iFFR in 10 patients, and excluded in 2 (sensitivity = 100%, 95% CI 69%-100%; specificity = 93%, 95% CI 78%-99%; NPV = 100%, 95% CI 88%-100%; PPV = 83%, 95% CI 57%-95%; accuracy = 95%, 95% CI 83%-99%). Revascularization was obtained through PCI in 9 patients and through CABG in the remaining patient. All patients, regardless of revascularization, received optimal medical therapy (OMT), including high-dose statins. Throughout a 1-year follow-up, the composite endpoint occurred in only 1 patient belonging to the revascularized group, who was admitted to our hospital for NSTEMI. No adverse events were observed among the negative-MRI patients and the positive-MRI not-revascularized patients. All patients remained free from angina. Conclusions According to current European guidelines, in our tertiary care center patients with CCS at intermediate risk first underwent CCTA. A stress MRI-based strategy for the evaluation of intermediate plaques led us to refine the selection of patients needing coronary revascularization. No events occurred in patients with negative MRI, highlighting the accuracy of CCTA plus stress MRI strategy in these patients. In all patients, OMT may have contributed to freedom from angina. FUNDunding Acknowledgement Type of funding sources: None.

Potential Biomarkers in Diagnosis, Prognosis and Prediction of Treatment Response in Malignant Glioma

Gliomas are the most common type of primary central nervous system malignancies with poor prognosis in adults. There are several challenges in developing a treatment protocol for this malignancy including presence of blood-brain barrier that inhibit drug delivery to brain tissue, drug and radiation resistance of tumor cells, and inter and intra-tumor heterogeneity of glioma. In addition, early treatment assessment is difficult for glioma patients because of phenomenon of pseudo-progression. Due to the challenges involved in treatment and monitoring of treatment response for glioma, it is very helpful to identify specific and non-invasive molecular and imaging markers in order to provide useful prognostic information. The aim of this article is to summarize several potential biological and imaging markers regarding malignant glioma. A brief description of the proteins involved in the glioma signaling pathways is provided in order to introduce potential biological markers. Furthermore, the role of imaging techniques in treatment management is discussed. Finally, correlation between tumor characteristics and values of angiogenesis and physiological factors measured in perfusion magnetic resonance imaging techniques as well as metabolites in MRS, and PET tracer’s uptake is investigated.

Arterial Spin Labeling Cerebral Perfusion Changes in Chronic Tinnitus With Tension-Type Headache

Purpose: Tinnitus is along with tension-type headache that will influence the cerebral blood flow (CBF) and accelerate the tinnitus severity. However, the potential associations between tension-type headache and tinnitus is still unknown. The current study will explore whether abnormal CBF exists in tinnitus patients and examine the effects of headache on CBF in tinnitus patients.Materials and Methods: Resting-state perfusion magnetic resonance imaging was performed in 40 chronic tinnitus patients and 50 healthy controls using pseudocontinuous arterial spin labeling. Regions with CBF differences between tinnitus patients and healthy controls were investigated. The effects of headache on tinnitus for CBF changes were further explored. Correlation analyses revealed the relationship between CBF values and tinnitus distress as well as CBF values and headache degree.Results: Relative to healthy controls, chronic tinnitus showed decreased CBF, mainly in right superior temporal gyrus (STG), left middle frontal gyrus (MFG), and left superior frontal gyrus (SFG); the CBF in the right STG and the left MFG was negatively correlated with THQ scores (r = −0.553, p = 0.001; r = −0.399, p = 0.017). We also observed a significant effect of headache on tinnitus for CBF in the right STG. Furthermore, the headache degree was correlated positively with tinnitus distress (r = 0.594, p = 0.020).Conclusion: Decreased CBF in auditory and prefrontal cortex was observed in chronic tinnitus patients. Headache may accelerate CBF reductions in tinnitus, which may form the basis for the neurological mechanism in chronic tinnitus with tension-type headache.

Correlation between amide proton transfer-related signal intensity and diffusion and perfusion magnetic resonance imaging parameters in high-grade glioma

Amide proton transfer (APT) imaging is a magnetic resonance (MR) molecular imaging technique that is sensitive to mobile proteins and peptides in living tissue. Studies have shown that APT-related signal intensity (APTSI) parallels with the malignancy grade of gliomas, allowing the preoperative assessment of tumor grades. An increased APTSI in malignant gliomas has been attributed to cytosolic proteins and peptides in proliferating tumor cells; however, the exact underlying mechanism is poorly understood. To get an insight into the mechanism of high APTSI in malignant gliomas, we investigated the correlations between APTSI and several MR imaging parameters including apparent diffusion coefficient (ADC), relative cerebral blood volume and pharmacokinetic parameters obtained in the same regions-of-interest in 22 high-grade gliomas. We found a significant positive correlation between APTSI and ADC (ρ = 0.625 and 0.490 for observers 1 and 2, respectively; p < 0.001 for both), which is known to be inversely correlated with cell density. Multiple regression analysis revealed that ADC was significantly associated with APTSI (p < 0.001 for both observers). Our results suggest possible roles of extracellular proteins and peptides in high APTSI in malignant gliomas.

Longitudinal Cerebral Blood Flow Changes in Normal Aging and the Alzheimer’s Disease Continuum Identified by Arterial Spin Labeling MRI

Background: Cross-sectional studies have shown lower cerebral blood flow (CBF) in Alzheimer’s disease (AD), but longitudinal CBF changes in AD are still unknown. Objective: To reveal the longitudinal CBF changes in normal control (NC) and the AD continuum using arterial spin labeling perfusion magnetic resonance imaging (ASL MRI). Methods: CBF was calculated from two longitudinal ASL scans acquired 2.22±1.43 years apart from 140 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). At the baseline scan, the cohort contained 41 NC, 74 mild cognitive impairment patients (MCI), and 25 AD patients. 21 NC converted into MCI and 17 MCI converted into AD at the follow-up. Longitudinal CBF changes were assessed using paired-t test for non-converters and converters separately at each voxel and in the meta-ROI. Age and sex were used as covariates. Results: CBF reductions were observed in all subjects. Stable NC (n = 20) showed CBF reduction in the hippocampus and precuneus. Stable MCI patients (n = 57) showed spatially more extended CBF reduction patterns in hippocampus, middle temporal lobe, ventral striatum, prefrontal cortex, and cerebellum. NC-MCI converters showed CBF reduction in hippocampus and cerebellum and CBF increase in caudate. MCI-AD converters showed CBF reduction in hippocampus and prefrontal cortex. CBF changes were not related with longitudinal neurocognitive changes. Conclusion: Normal aging and AD continuum showed common longitudinal CBF reductions in hippocampus independent of disease and its conversion. Disease conversion independent longitudinal CBF reductions escalated in MCI subjects.