EXTH-07. TEMPORAL ASSESSMENT OF ALTERED PERI-ABLATION BLOOD-BRAIN BARRIER PERMEABILITY FOLLOWING TUMOR CYTOREDUCTION BY THERMAL THERAPY IN A RAT ORTHOTOPIC GLIOBLASTOMA MODEL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi164-vi164
Author(s):  
Tavarekere Nagaraja ◽  
Seamus Bartlett ◽  
Glauber Cabral ◽  
Katelynn Farmer ◽  
Robert Knight ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Evans Blue ◽  
Thermal Therapy ◽  
Female Rats ◽  
Brain Barrier ◽  
Gadolinium Contrast ◽  
Dce Mri ◽  
Blood Brain ◽  
Bbb Permeability ◽  
Bbb Opening

Abstract Laser interstitial thermal therapy (LITT) is a minimally invasive tumor cytoreductive treatment for recurrent gliomas, brain tumors in eloquent regions and/or otherwise inaccessible. Following reports of persistent peri-ablation blood-brain barrier (BBB) opening in humans, we examined this phenomenon using a rat glioblastoma model. Athymic female rats were implanted with U251 tumor cells in one brain hemisphere. Tumor growth was monitored using magnetic resonance imaging (MRI) and dynamic contrast enhanced (DCE)-MRI. When tumors reached about 4 mm in diameter, they were ablated under supervision of diffusion-weighted MRI using Visualase®, a clinical LITT system. Four rats were used as controls. Longitudinal MRI data were obtained before LITT, and at post-LITT 2 (n=9), 3 (n=3) and 4 (n=9) weeks. After the terminal MRI at each time point, rats were injected intravenously with fluorescent isothiocyanate dextran (FITC-dextran; 2000 kDa) and Evans Blue (68 kDa after binding to plasma albumin) and the brains immersion fixed in 10% paraformaldehyde. The brains were cut into 100 μM thick slices in a vibratome and examined for the distribution of the two fluorophores. All rats survived the LITT procedure. The sham controls showed increased tumor burden by 2 weeks and were sacrificed. DCE-MRI data and fluorescent data showed elevated BBB permeability in peri-ablation regions, with leakage of a gadolinium contrast on DCE-MRI and of Evans Blue, but not of FITC-dextran. Histology showed little tumor tissue at 2 weeks, but evidence of recurrence at ablation margins at later times. These data demonstrate that LITT is adaptable to rat glioma models and can be performed under MRI monitoring. Peri-ablation regions showed selective increase in BBB permeability acutely due to sublethal heating, but later increases in permeability may be due to tumor recurrence. We suggest this model is useful for examining the temporal and spatial development of peri-ablation BBB opening following LITT.

scholarly journals SCIDOT-50. A RAT MODEL FOR LASER INTERSTITIAL THERMAL THERAPY FOR GLIOBLASTOMA: EFFECTS ON PERI-ABLATION BLOOD-BRAIN BARRIER AND IMPLICATIONS FOR POST-ABLATION CHEMOTHERAPY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi282-vi282
Author(s):  
Tavarekere Nagaraja ◽  
James Ewing ◽  
Katelynn Farmer ◽  
Grahm Valadie ◽  
Stephen Brown ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Blood Brain Barrier ◽  
Thermal Therapy ◽  
Female Rats ◽  
Brain Barrier ◽  
Laser Interstitial Thermal Therapy ◽  
Lethal Temperatures ◽  
Blood Brain ◽  
U251 Cells ◽  
Bbb Opening

Abstract Laser interstitial thermal therapy (LITT) is a minimally invasive tumor cytoreductive treatment for recurrent gliomas, brain tumors in eloquent regions or otherwise inaccessible to traditional open surgery. LITT offers quicker recovery and shorter hospital stays as additional advantages. A laser fiberoptic catheter is positioned in the body of the tumor under magnetic resonance imaging (MRI) guidance via a twist drill hole in the skull. Using MR thermometry, the tumor is ablated by laser heating to lethal temperatures. The peri-ablation zones get heated to sub-lethal temperatures and subsequently recover. It has been reported in humans that opening of the blood-brain barrier (BBB) occurs, lasting several weeks after ablation. We have adapted Visualase®, a clinically available LITT system, for use in a rat glioblastoma model. Athymic female rats (n=7) were implanted with U251 tumor cells in one brain hemisphere. Tumor growth was monitored using MRI. When tumors reached about 4 mm in diameter, they were ablated under supervision of MR diffusion-weighted MRI, sparing the surrounding normal brain tissue. Contrast-enhanced MRI data were obtained before LITT, immediately after and at post-LITT 24 h. The brains were processed for histopathology and stained with hematoxylin and eosin (H&E) for visualizing the extent of the tumor and for major histocompatibility complex (MHC) to identify the human-derived U251 cells. All rats survived the LITT procedure. A ring of contrast enhancement around ablation perimeter was observed immediately after, and also at 24 h. H&E data showed near-complete ablation of the tumors. However, MHC staining showed U251 cells still remaining in the ablation vicinity. These data suggest this model is useful for examining the temporal and spatial development of peri-ablation BBB opening following LITT. Concurrent timing of post-ablation chemotherapy to the development and presence of post-LITT BBB opening may aid in efficient targeting of remaining tumor cells.

scholarly journals EXTH-02. THE BLOOD BRAIN BARRIER (BBB) PERMEABILITY IS ALTERED BY TUMOR TREATING FIELDS (TTFIELDS) IN VIVO

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi82-vi82 ◽  
Author(s):  
Ellina Schulz ◽  
Almuth F Kessler ◽  
Ellaine Salvador ◽  
Dominik Domröse ◽  
Malgorzata Burek ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Dce Mri ◽  
Tumor Treating Fields ◽  
Blood Brain ◽  
Vessel Structure ◽  
Bbb Permeability ◽  
The Brain

Abstract OBJECTIVE For glioblastoma patients Tumor Treating Fields (TTFields) have been established as adjuvant therapy. The blood brain barrier (BBB) tightly controls the influx of the majority of compounds from blood to brain. Therefore, the BBB may block delivery of drugs for treatment of brain tumors. Here, the influence of TTFields on BBB permeability was assessed in vivo. METHODS Rats were treated with 100 kHz TTFields for 72 h and thereupon i.v. injected with Evan’s Blue (EB) which directly binds to Albumin. To evaluate effects on BBB, EB was extracted after brain homogenization and quantified. In addition, cryosections of rat brains were prepared following TTFields application. The sections were stained for tight junction proteins Claudin-5 and Occludin and for immunoglobulin G (IgG) to assess vessel structure. Furthermore, serial dynamic contrast-enhanced DCE-MRI with Gadolinium contrast agent was performed before and after TTFields application. RESULTS TTFields application significantly increased the EB accumulation in the rat brain. In TTFields-treated rats, the vessel structure became diffuse compared to control cryosections of rat brains; Claudin 5 and Occludin were delocalized and IgG was found throughout the brain tissue. Serial DCE-MRI demonstrated significantly increased accumulation of Gadolinium in the brain, observed directly after 72 h of TTFields application. The effect of TTFields on the BBB disappeared 96 h after end of treatment and no difference in contrast enhancement between controls and TTFields treated animals was detectable. CONCLUSION By altering BBB integrity and permeability, application of TTFields at 100 kHz may have the potential to deliver drugs to the brain, which are unable to cross the BBB. Utilizing TTFields to open the BBB and its subsequent recovery could be a clinical approach of drug delivery for treatment of brain tumors and other diseases of the central nervous system. These results will be further validated in clinical Trials.

scholarly journals P11.28 Alteration of blood brain barrier (BBB) permeability by Tumor Treating Fields (TTFields) in vivo

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii49-iii49
Author(s):  
A F Keßler ◽  
E Salvador ◽  
D Domröse ◽  
M Burek ◽  
C Tempel Brami ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Dce Mri ◽  
Tumor Treating Fields ◽  
Blood Brain ◽  
Vessel Structure ◽  
Bbb Permeability ◽  
The Brain

Abstract BACKGROUND Alternating electric fields with intermediate frequency (100 - 300 kHz) and low intensity (1 - 3 V/cm), known as Tumor Treating Fields (TTFields), have been established as a novel adjuvant therapy for glioblastoma (GBM) patients. The blood brain barrier (BBB) tightly controls the influx of the majority of compounds from blood to brain. Due to this regulation, the BBB may block delivery of drugs for treatment of brain tumors, in particular GBM. In this study, we investigated the influence of TTFields on BBB permeability in vivo. MATERIAL AND METHODS For determination of BBB permeability, rats were treated with 100 kHz TTFields for 72 h. At the end of treatment, rats were i.v. injected with Evan′s Blue (EB), which binds Albumin (~70 kDa) upon injection to the blood. EB was extracted after brain homogenization and quantified at 610 nm. In addition, cryosections of rat brains were prepared following TTFields application at 100 kHz for 72 h, and sections were stained for Claudin 5, Occludin and immunoglobulin G (IgG) to assess vessel structure. Moreover, serial dynamic contrast-enhanced DCE-MRI with Gadolinium contrast agent (Gd) was performed before and after TTFields application. RESULTS In vivo, the EB accumulation in the brain was significantly increased by application of TTFields to the rat head. Claudin 5 and Occludin staining was visible in vessel endothelial cells and localized at the cells’ edges in control cryosections of rat brains. In TTFields-treated rats, the vessel structure became diffuse; Claudin 5 and Occludin were delocalized and IgG was found throughout the brain tissue and not solely inside the vessels, as it is normally the case. Serial DCE-MRI demonstrated significantly increased accumulation of Gd in the brain, detected directly after 72 h of TTFields application. 96 h after end of TTFields treatment the effect on the BBB disappeared and no difference in contrast enhancement between controls and TTFields treated animals was observable. CONCLUSION Application of TTFields at 100 kHz could have the potential to deliver drugs to the brain, which normally are unable to cross the BBB by altering BBB integrity and permeability. Utilizing TTFields to open the BBB and its subsequent recovery, as demonstrated by the data presented herein, could lead to a clinical approach of drug delivery for treatment of malignant brain tumors and other diseases of the central nervous system. These results will be further validated in clinical trials.

Opening of the Blood-Brain Barrier by Intravenous Contrast Media in Euvolemic and Dehydrated Rabbits

1989 ◽  
Vol 30 (4) ◽  
pp. 439-444 ◽  
Author(s):  
K. Hayakawa ◽  
T. M. Morris ◽  
R. W. Katzberg
Keyword(s):  
Contrast Media ◽  
Blood Brain Barrier ◽  
Evans Blue ◽  
Plasma Osmolality ◽  
Iodine Concentration ◽  
Brain Barrier ◽  
Blue Staining ◽  
Intravenous Contrast ◽  
Blood Brain ◽  
Bbb Opening

It has been suggested that intravenous injections of hypertonic contrast media when used in computed tomography and digital subtraction angiography might raise plasma osmolality sufficiently to open the blood-brain barrier (BBB). The current investigation establishes the threshold of plasma osmolality that causes the the opening of the BBB in euvolemic and dehydrated rabbits. Euvolemic rabbits were allowed food and water ad libitum. Dehydrated rabbits received 4.0 mg/kg of furosemide intramuscularly and were deprived of water for 72 hours. Meglumine/sodium diatrizoate 76 per cent (n=28) or mannitol 20 per cent (n= 12) was administrated intravenously, at a rate of 25 mmol/kg body weight/hour for 2, 3 or 4 hours. Plasma osmolality, blood iodine concentration, blood pressure, heart rate and hematocrit were assessed at regular intervals. Evans blue and 99Tcm-DTPA were used simultaneously as tracers for BBB opening. Rating of BBB opening with 99Tcm-DTPA correlated well with Evans blue staining (r=0.863, p<0.001; n=42). BBB opening was related to plasma osmolality and was similar for both contrast media and mannitol. Widespread BBB opening occurred above 400 mmol/kg while focal BBB opening occurred above 370 mmol/kg. Dehydration per se increased plasma osmolality but did not reduce the threshold for BBB opening.

scholarly journals Blood–Brain Barrier Repair of Bevacizumab and Corticosteroid as Prediction of Clinical Improvement and Relapse Risk in Radiation-Induced Brain Necrosis: A Retrospective Observational Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Ruiqi Xue ◽  
Meiwei Chen ◽  
Jinhua Cai ◽  
Zhenhong Deng ◽  
Dong Pan ◽  
...  
Keyword(s):  
Treatment Response ◽  
Blood Brain Barrier ◽  
Therapeutic Effect ◽  
Brain Barrier ◽  
Dce Mri ◽  
Brain Necrosis ◽  
Blood Brain ◽  
Radiation Induced ◽  
Bbb Permeability ◽  
Volume Decrease

BackgroundBlood–brain barrier (BBB) disruption after endothelial damage is a crucial part of radiation-induced brain necrosis (RN), but little is known of BBB disruption quantification and its role in the evaluation of therapeutic effect and prognosis for drug treatment. In this retrospective study, BBB repair by bevacizumab and corticosteroid and the correlation between BBB permeability and treatment response and relapse were evaluated by dynamic contrast-enhanced MRI (DCE-MRI).MethodsForty-one patients with RN after radiotherapy for nasopharyngeal carcinoma (NPC) (28 treated with bevacizumab and 13 with corticosteroid), 12 patients with no RN after NPC radiotherapy, and 12 patients with no radiotherapy history were included as RN, non-RN, and normal groups, respectively. DCE-MRI assessed BBB permeability in white matter of bilateral temporal lobe. DCE parameters were compared at baseline among the three groups. DCE parameters after treatment were compared and correlated with RN volume decrease, neurological improvement, and relapse.ResultsThe extent of BBB leakage at baseline increased from the normal group and non-RN group and to RN necrosis lesions, especially Ktrans (Kruskal–Wallis test, P &lt; 0.001). In the RN group, bevacizumab-induced Ktrans and ve decrease in radiation necrosis lesions (both P &lt; 0.001), while corticosteroid showed no obvious effect on BBB. The treatment response rate of bevacizumab was significantly higher than that of corticosteroid [30/34 (88.2%) vs. 10/22 (45.4%), P &lt; 0.001]. Spearman analysis showed baseline Ktrans, Kep, and vp positively correlated with RN volume decrease and improvement of cognition and quality of life in bevacizumab treatment. After a 6-month follow-up for treatment response cases, the relapse rate of bevacizumab and corticosteroid was 10/30 (33.3%) and 2/9 (22.2%), respectively, with no statistical difference. Post-bevacizumab Ktrans level predicted relapse in 6 months with AUC 0.745 (P &lt; 0.05, 95% CI 0.546–0.943, sensitivity = 0.800, specificity = 0.631).ConclusionsBevacizumab improved BBB leakage in RN necrosis. DCE parameters may be useful to predict therapeutic effect and relapse after bevacizumab.

Influence of respiratory stress and hypertension upon the blood-brain barrier

1980 ◽  
Vol 53 (5) ◽  
pp. 666-673 ◽  
Author(s):  
Joe Sam Robinson ◽  
Robert A. Moody
Keyword(s):  
Blood Brain Barrier ◽  
Blood Gases ◽  
Brain Barrier ◽  
Control Group ◽  
Arterial Blood Gases ◽  
White Rats ◽  
Arterial Blood ◽  
Blood Brain ◽  
Bbb Permeability ◽  
Bbb Opening

✓ The effects of acute hypertension and respiratory stress induced by Aramine (metaraminol bitartrate) upon blood-brain barrier (BBB) permeability to horseradish peroxidase (HRP) were studied in adult inbred white rats. The BBB permeability was quantitated by slicing the brain of each animal into 500-µ thick sections, incubating the sections using the Reese-Karnovsky method, and counting all observed HRP perivascular exudates. No evidence of BBB compromise or significant elevation of blood pressure (BP) was observed in the following experimental groups: 1) control group of five animals; 2) hyperventilated group of five animals (final mean arterial blood gases: pO2, 104.2 mm Hg; pCO2, 24.8 mm Hg; pH, 7.53); 3) anoxicstress group of five animals (final mean arterial blood gases: pCO2, 31.4 mm Hg; pCO2, 58.2 mm Hg; pH, 7.21). However, in a group of 15 animals subjected to anoxic stress followed by hyperventilation, in addition to extreme changes in the levels of arterial blood gases, a significant BP increase occurred (mean BP increase per second, 3.43 ± 0.25 mm Hg; final mean BP, 163.3 ± 3.18 mm Hg); as well as significant BBB opening (mean number of HRP exudates per animal, 12.2 ± 0.85). Likewise, a final group of 10 animals given intravenous Aramine displayed a significant systemic BP elevation (mean BP increase per second, 6.9 ± 0.38 mm Hg; final mean BP, 165.8 ± 3.16 mm Hg), accompanied by BBB opening (mean number of exudates per animal, 51.5 ± 5.95). The variable most strongly associated with the degree of barrier opening was the rate of BP rise (correlation coefficient = + 0.84).

DCE-MRI blood–brain barrier assessment in acute ischemic stroke

Neurology ◽  
2016 ◽  
Vol 88 (5) ◽  
pp. 433-440 ◽  
Author(s):  
Kersten Villringer ◽  
Borja E. Sanz Cuesta ◽  
Ann-Christin Ostwaldt ◽  
Ulrike Grittner ◽  
Peter Brunecker ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Symptom Onset ◽  
Brain Barrier ◽  
Stroke Patients ◽  
Dce Mri ◽  
Link Type ◽  
Blood Brain ◽  
Bbb Permeability

Objective:To quantitatively evaluate blood–brain barrier changes in ischemic stroke patients using dynamic contrast-enhanced (DCE) MRI.Methods:We examined 54 stroke patients (clinicaltrials.govNCT00715533, NCT02077582) in a 3T MRI scanner within 48 hours after symptom onset. Twenty-eight patients had a follow-up examination on day 5–7. DCE T1 mapping and Patlak analysis were employed to assess BBB permeability changes.Results:Median stroke Ktrans values (0.7 × 10−3 min−1 [interquartile range (IQR) 0.4–1.8] × 10−3 min−1) were more than 3-fold higher compared to median mirror Ktrans values (0.2 × 10−3 min−1, IQR 0.1–0.7 × 10−3 min−1, p < 0.001) and further increased at follow-up (n = 28, 2.3 × 10−3 min−1, IQR 0.8–4.6 × 10−3 min−1, p < 0.001). By contrast, mirror Ktrans values decreased over time with a clear interaction of timepoint and stroke/mirror side (p < 0.001). Median stroke Ktrans values were 2.5 times lower than in hemorrhagic transformed regions (0.7 vs 1.8 × 10−3 min−1; p = 0.055). There was no association between stroke Ktrans values and the delay from symptom onset to baseline examination, age, and presence of hyperintense acute reperfusion marker.Conclusion:BBB in acute stroke patients can be successfully assessed quantitatively. The decrease of BBB permeability in unaffected regions at follow-up may be an indicator of global BBB leakage even in vessel territories remote from the index infarct.

scholarly journals Cerebral Ischemia–Reperfusion Injury in Rats—A 3 T MRI Study on Biphasic Blood–Brain Barrier Opening and the Dynamics of Edema Formation

2009 ◽  
Vol 29 (11) ◽  
pp. 1846-1855 ◽  
Author(s):  
Deepu R Pillai ◽  
Michael S Dittmar ◽  
Dobri Baldaranov ◽  
Robin M Heidemann ◽  
Erica C Henning ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Ischemia Reperfusion Injury ◽  
Vasogenic Edema ◽  
Ischemia Reperfusion ◽  
Brain Barrier ◽  
Edema Formation ◽  
Temporal Shift ◽  
Blood Brain ◽  
Bbb Permeability ◽  
Bbb Opening

Serial magnetic resonance imaging (MRI) was performed to investigate the temporal and spatial relationship between the biphasic nature of blood–brain barrier (BBB) opening and, in parallel, edema formation after ischemia–reperfusion (I/R) injury in rats. T2-weighted imaging combined with T2-relaxometry, mainly for edema assessment, was performed at 1 h after ischemia, after reperfusion, and at 4, 24 and 48 h after reperfusion. T1-weighted imaging was performed before and after gadolinium contrast at the last three time points to assess BBB integrity. The biphasic course of BBB opening with a significant reduction in BBB permeability at 24 h after reperfusion, associated with a progressive expansion of leaky BBB volume, was accompanied by a peak ipsilateral edema formation. In addition, at 4 h after reperfusion, edema formation could also be detected at the contralateral striatum as determined by the elevated T2-values that persisted to varying degrees, indicative of widespread effects of I/R injury. The observations of this study may indicate a dynamic temporal shift in the mechanisms responsible for biphasic BBB permeability changes, with complex relations to edema formation. Stroke therapy aimed at vasogenic edema and drug delivery for neuroprotection may also be guided according to the functional status of the BBB, and these findings have to be confirmed in human stroke.

scholarly journals THER-11. PEPTIDE-MEDIATED PERMEABILIZATION OF THE BLOOD-BRAIN BARRIER IMPROVES DRUG DELIVERY TO BRAIN METASTASIS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i13-i13
Author(s):  
Synnøve Nymark Aasen ◽  
Heidi Espedal ◽  
Christopher Holte ◽  
Olivier Keunen ◽  
Tine Veronika Karlsen ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Plasma Membranes ◽  
Combined Treatment ◽  
Brain Barrier ◽  
Therapeutic Window ◽  
Dce Mri ◽  
Blood Brain ◽  
The Brain ◽  
Bbb Opening

Abstract BACKGROUND: Melanoma patients have a high risk of developing brain metastases, which is associated with a poor prognosis. The blood-brain barrier (BBB) inhibits sufficient drug delivery into metastatic lesions. We investigated the ability of a synthetic peptide (K16ApoE) to permeabilize the BBB for more effective drug treatment. METHODS: DCE-MRI was performed to study the therapeutic window of BBB opening facilitated by K16ApoE. In vivoand in vitroassays were used to determine K16ApoE toxicity and also to obtain mechanistic insight into its action on the BBB. The therapeutic impact of K16ApoE on melanoma metastases was determined together with dabrafenib, which is otherwise known not to cross an intact BBB. RESULTS: DCE-MRI exhibited an effective K16ApoE-mediated BBB opening for up to 1h. Mechanistic studies displayed a dose-dependent effect of K16ApoE caused by induction of endocytosis. At higher concentrations, the peptide also showed unspecific disturbances on plasma membranes. Combined treatment with K16ApoE and dabrafenib reduced the brain metastatic burden in mice compared to dabrafenib. We also showed by PET/CT that the peptide facilitated the delivery of compounds up to 150 kDa into the brain. CONCLUSIONS: We demonstrate a transient opening of the BBB, caused by K16ApoE, that facilitates improved drug-delivery into the brain. This improves the efficacy of drugs that otherwise do not cross the intact BBB.

WED 168 Blood-brain barrier imaging with dynamic contrast-enhanced mri

2018 ◽  
Vol 89 (10) ◽  
pp. A21.2-A21
Author(s):  
Varatharaj Aravinthan ◽  
Liljeroth Maria ◽  
Darekar Angela ◽  
BW Larsson Henrik ◽  
Galea Ian ◽  
...  
Keyword(s):  
White Matter ◽  
Blood Brain Barrier ◽  
Cerebral Blood Volume ◽  
Brain Barrier ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Normal Appearing White Matter ◽  
Blood Brain ◽  
Contrast Enhanced ◽  
Bbb Permeability

BackgroundDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can detect subtle blood-brain barrier (BBB) permeability. We developed a protocol and conducted experiments to validate the technique.Methods12 subjects with relapsing-remitting multiple sclerosis (RRMS) and 13 controls were recruited. Whole-brain 3D DCE-MRI at 3 Tesla was used to calculate the influx constant Ki (Patlak method). Values were derived for manual regions of interest (ROI) as well as segmented tissue masks. In controls, cerebral blood volume (CBV) was measured in grey and white matter.ResultsIn RRMS, Ki in visibly-enhancing lesions was significantly higher than in normal-appearing white matter (NAWM) (p=0.002). Ki in NAWM was significantly higher in RRMS than controls, by both ROI (p=0.014) and segmentation (p=0.019) methods. In controls, Ki was significantly higher in grey than white matter (p=0.001). CBV (and therefore vascular surface area) was also significantly higher in grey matter (p=0.005), with a mean ratio of 1.9.ConclusionsOur method produces results in line with the expected behaviour of a BBB permeability marker, and the grey/white matter CBV ratio is in agreement with the histologically-established value.

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