rCBV Reduction Research Articles

Association of SDF1 inhibition with local control and relative cerebral blood volume of glioblastoma.

2058 Background: Glioblastoma is the most common and aggressive primary brain tumor, with 75-85% of patients historically having recurrence within the original tumor site. We have shown in preclinical studies that inhibition of the SDF1/CXCR4 pathway by the CXCR4 inhibitor Plerixafor increases tumor response to irradiation by inhibition of the recovery of tumor blood vessels. Methods: Newly diagnosed glioblastoma patients were enrolled to the clinical trial using the investigational agent Plerixafor after standard radiation therapy and temozolomide (NCT01977677). To date, 28 patients out of the planned accrual of 29 have been enrolled to this study. Normalized relative cerebral blood volume (rCBV) ratios were calculated by the mean rCBV within the 95% isodose radiation field one month post-radiation as compared to contralateral white matter outside of the radiation field. Our imaging analysis compares patients treated with Plerixafor compared to a control group receiving standard therapy (chemo-RT). Results: There was a significant reduction in rCBV measured by DSC-MRI within the 95% isodose field one month after radiation therapy in patients receiving Plerixafor compared to control (p < 0.02). The rCBV out of the radiation field was similar between patients receiving Plerixafor compared to control patients one-month post radiation therapy. As of February 7, 2017, only 2 of the total of 9 recurrences occurred within the irradiated field. The rate of out of field recurrence (77%) was therefore much higher than expected (20%), with statistical significance (p < 0.03, Fisher’s exact test). Conclusions: We show that Plerixafor has a meaningful impact on local control of glioblastoma. Furthermore, DSC-MRI could be a useful biomarker of its efficacy.

The application of cerebral blood volume software inassessing the cerebral blood volume comparative study on the clinical manifestations before and afterballoon occlusion testwith hypotension

Objective To discuss the application of cerebral blood volume software in assessing thecerebral blood volume (CBV) comparative study on the clinical manifestations before and after balloon occlusion test with hypotension.Aiming to find an objective indicator for balloon occlusion test with hypotensionwhich is the gold standard of occluding internal carotid artery (ICA).Methods 10 patients diagnosed with cerebrovascular disease through digital subtraction angiography (DSA) whounderwent balloon occlusion test (BOT) with hypotension from October 2012 to October 2013,including8 cases of carotid cavernous sinus (CCF),1 case of Giant aneurysm on ICA cavernous sinus segment,and 1 case of CCF and pseudoaneurysm.CBV maps were acquiredinSoftware Cerebral Blood Volumeby manual injection of 60 ml CM (370 g/L) before and after balloon occlusion test with hypotension within 15 minutes,from which mean relative CBV (rCBV) of regions of interest (ROIs) was comparedin the same axial view,The change of mean rCBV was compared with the change of clinical manifestations before and after Ballon Occlusion Test with hypotension.Results There were 10 patients were involved inthis study,of which,no ischemic complicationswere recognized in 8 patients.Good perfusion symmetry was detected with averaged rCBV 1.02 ± 0.06.in those 8 patients,1 patient underwent permanent ICA occlusion with a detachable balloonwithout acute or delayed neurologic deficit perceived.The others underwent nidus embolization with coils with keeping ICAunobstructed and got well recovered.Two patients failed to tolerate the BOT testwith hypotensionwho developed in disturbance of consciousness and the contralateral limb hemiplegia.CBVs from the affected hemisphere was significantly lower than those from the unaffected hemisphere in the corresponding regions with mean rCBV reduction close to 24％ and 21％.2 patients underwent nidus embolization with coils with keeping ICA unobstructed and got well recovered.Conclusion CBV maps have a good consistency with clinical manifestationsbefore and after balloonocclusion testwith hypotension.It can be an objective indicator for the gold standard of occluding ICA. Key words: Cerebral blood volume software; Cerebral blood volume; Balloon occlusion test with hypotension; Carotid-cavernous sinus

Assessment of perihematomal hypoperfusion injury in subacute and chronic intracerebral hemorrhage by CT perfusion imaging

Objective: To study alterations of perihematomal cerebral perfusion associated to subacute and chronic intracerebral hemorrhage (ICH) by means of computed tomography perfusion (CTP) imaging.Methods: Non-enhanced CT scan and CTP examination were performed in 12 patients with subacute and chronic supratentorial ICH. The hematoma volume was measured, and the regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), mean transit time (MTT) and time-to-peak (TTP) adjacent to hematoma were measured in 11 of 12 cases.Results: Eleven patients with mean age of 58·1 years were finally analysed. Mean time interval from symptom onset to initial CTP scanning was 18·4 days; mean hematoma volume was 26·8 ml. The gradient of hypoperfusion around the hematoma was revealed by rCBF maps in 11 cases, and by rCBV maps in ten cases. The areas of delayed TTP and MTT were showed in 11 and ten cases, respectively. The degree of reduction in rCBV correlated strongly with the hematoma volume (rinner=0·764, p=0·006;router=0·703, p=0·016). There was no correlation between the changes in rCBF, rCBV, MTT and TTP and the time interval from symptom onset to initial CTP examination.Conclusion: We have concluded that the gradient of hypoperfusion surrounding the hematoma may still exist during the subacute and chronic phases after ICH. The alterations in rCBV correlate with the hematoma volume. We believe that the reperfusion injury marked by increased rCBV contributes to the perilesional brain injury. The quantitative CT perfusion measurements can provide valuable information in individual management and prognostic evaluation of ICH.

Early Radiotherapy Dose Response and Lack of Hypersensitivity Effect in Normal Brain Tissue: a Sequential Dynamic Susceptibility Imaging Study of Cerebral Perfusion

Aims To determine if magnetic resonance perfusion markers can be used as an analytical marker of subclinical normal brain injury after radiotherapy, by looking for a dose–effect relationship. Materials and methods Four patients undergoing conformal radiotherapy to 54 Gy in 30 fractions for low-grade gliomas were imaged with conventional T 2-weighted and fluid attenuated inversion recovery imaging as well as dynamic contrast susceptibility perfusion imaging. Forty regions of interest were determined from the periventricular white matter. All conventional sequences were examined for evidence of radiation-induced changes. Patients were imaged before radiotherapy, after one fraction, at the end of treatment and then at 1 and 3 months from the end of radiotherapy. For each region the relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and mean transit time (MTT) expressed as a ratio of the baseline value, and radiotherapy dose were determined. Results Of the 40 regions, seven occurred within the gross tumour volume and a further four occurred in regions later infiltrated by tumour, and were thus excluded. Regions within the 80% isodose showed a reduction in rCBV and rCBF over the 3 month period. There was no significant alteration in rCBV or rCBF in regions outside the 60% isodose (i.e. <32 Gy). MTT did not alter in any region. There seemed to be a threshold effect at 132 days from the end of radiotherapy of 47% (standard error of the mean 11.5, about 25.4 Gy) for rCBV and 59% (standard error of the mean 14.2, about 31.9 Gy) for rCBF. Conclusions There was a dose-related reduction in rCBV and rCBF in normal brain after radiotherapy at higher dose levels. Although this study used a limited number of patients, it suggests that magnetic resonance perfusion imaging seems to act as a marker of subclinical response of normal brain and that there is an absence of an early hypersensitivity effect with small doses per fraction. Further studies are required with larger groups of patients to show that these results are statistically robust.

Relationship between alternation of cerebral blood flow and formation of brain edema around the hematoma after experimental intracerebral hemorrhage

Objective To investigate the mechanism of brain edema formation around the hematoma and the relationship between the formation of brain edema and the changes of regional cerebral blood flow after intracerebral hemorrhage (ICH) in rats, and to provide experimental basis for the clinical treatment of ICH . Methods Seventy male Sprague-Dawley rats were randomly divided into ICH groups and sham-operated groups. ICH was produced by microinjection of 40 ul fresh autologous blood or saline into the right caudatum. Dynamic CT perfusion imaging was performed, and the parameters of regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), and mean transit time (MTT) around the hematoma were calculated respectively. Then the rats were sacrificed, and the water content, sodium, potassium, and calcium concentrations were measured respectively. The correlative study between the water content and rCBF and rCBV were carried out. Results The gradient of perihematomal hypoperfusion was revealed on CT perfusion maps in ICH groups. The alternation of rCBF around the hematomas were fluctuated, and rCBF reduction was most pronounced at 1 hour afer ICH, then the rCBF gradually returned, reaching the peaks at 6 hours and 24 hours after ICH, respectively. In the meantime, rCBV reduction around the hematoma was most pronounced at 1 hour after ICH. Then the rCBV gradually increased, and reaching the peak at 24 hours. The water contents were gradually increased in the ipsilateral basal ganglia in the animals sacrificed at 6, 24, and 72 hours. The accumulation of water was at its peak at 24 hours, and remained in the animals sacrificed at the 72 hours. The perihemorrhagic water contents correlated significantly with rCBV surrounding hematomas, r=0.372(one-tailed), P0.05. Conclusion The perihemorrhagic brain edema results from the common effects of the blood-brain-barrier disruption, cytotoxic edema, and the accumulation of osmotically active substances. The rCBF reduction occured in the early stage of ICH and the rCBV compensatory increase play important roles in producing vasogenic edema. Perfusion CT and its parameter analysis is a suitable method in the study of the relationship between the formation of brain edema and the changes of regional cerebral blood flow after intracerebral hemorrhage in vivo.

Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes.

Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO2), oxygen extraction fraction (rOEF), and cerebral blood volume (rCBV) were investigated using positron emission tomography (PET) in 16 patients with senile dementia of Alzheimer's type (SDAT), and compared with those of 6 nondemented and 3 demented patients with deep white matter high signal (DWMH) on T2-weighted MRI and 6 controls. rCBF, rCMRO2 and rCBV were determined using C15O2, 15O2 and C15O, respectively. rCBF and CMRO2 were significantly decreased in the frontal, parietal and temporal cortex (P < 0.05) in patients with SDAT, and showed a significant correlation with the severity of dementia (P < 0.05). In patients with DWMH rCBF was significantly decreased in the parietal cortex and in the frontal white matter in nondemented patients, and in the cerebral cortex and white matter of most regions studied in demented patients (P < 0.05), whereas rCMRO2 was significantly reduced in only the frontal and temporal cortex of demented patients (P < 0.05). rOEF was significantly increased in the parietal cortex of patients with SDAT and in the white matter of patients with SDAT or DWMH (P < 0.05), and the increase in the frontal white matter significantly paralleled the progression of dementia in patients with SDAT (P < 0.05). rCBV was significantly decreased in the parietal and temporal cortex of patients with SDAT (P < 0.05), but not in any areas of those with DWMH. These results suggest that rOEF is increased in both SDAT and patients with DWMH. The increase in rOEF in patients with SDAT may be accounted for by reduction in rCBV resulting from decreased activity in the vasodilatory cholinergic system, impairment of glucose metabolism and white matter changes; the rOEF increase in patients with DWMH suggests relative preservation of oxidative metabolism compared to disturbed perfusion.