scholarly journals The effect of imatinib therapy on tumour cycling hypoxia, tissue oxygenation and vascular reactivity

2017 ◽  
Vol 2 ◽  
pp. 38
Author(s):  
Miguel R. Gonçalves ◽  
Sean Peter Johnson ◽  
Rajiv Ramasawmy ◽  
Mark F. Lythgoe ◽  
R. Barbara Pedley ◽  
...  

Background: Several biomedical imaging techniques have recently been developed to probe hypoxia in tumours, including oxygen-enhanced (OE) and blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI). These techniques have strong potential for measuring both chronic and transient (cycling) changes in hypoxia, and to assess response to vascular-targeting therapies in the clinic. Methods: In this study, we investigated the use of BOLD and OE-MRI to assess changes in cycling hypoxia, tissue oxygenation and vascular reactivity to hyperoxic gas challenges, in mouse models of colorectal therapy, following treatment with the PDGF-receptor inhibitor, imatinib mesylate (Glivec). Results: Whilst no changes were observed in imaging biomarkers of cycling hypoxia (from BOLD) or chronic hypoxia (from OE-MRI), the BOLD response to carbogen-breathing became significantly more positive in some tumour regions and more negative in other regions, thereby increasing overall heterogeneity. Conclusions: Imatinib did not affect the magnitude of cycling hypoxia or OE-MRI signal, but increased the heterogeneity of the spatial distribution of BOLD MRI changes in response to gas challenges.

2021 ◽  
pp. 1-11
Author(s):  
Fen Chen ◽  
Han Yan ◽  
Fan Yang ◽  
Li Cheng ◽  
Siwei Zhang ◽  
...  

<b><i>Background:</i></b> Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) has been widely used to assess renal oxygenation changes in different kidney diseases in recent years. This study was designed to evaluate and compare renal tissue oxygenation using 2 BOLD-MRI analysis methods, namely, the regional and whole-kidney region of interest (ROI) selection methods. <b><i>Methods:</i></b> The study ended up with 10 healthy controls and 40 chronic kidney disease (CKD) patients without dialysis. Their renal BOLD-MRI data were analyzed using whole-kidney ROI selection method and compared with regional ROI selection method. <b><i>Results:</i></b> We found the cortical, medullary, and whole-kidney R2* values were significantly higher in CKD patients than those in controls. Compared with the regional ROI selection method, the whole-kidney ROI selection method yielded higher cortical R2* values in both controls and CKD patients. The whole-kidney R2* values of deteriorating renal function group were significantly higher than those in stable renal function group. <b><i>Conclusions:</i></b> Cortical and medullary oxygenation was decreased significantly in CKD patients compared with the healthy controls, particularly in the medulla. The whole-kidney R2* values were positively correlated with kidney function and inversely correlated with the estimated glomerular filtration rate and effective renal plasma flow. Whole-Kidney R2* value might effectively predict the progression of renal function in patients with CKD.


2014 ◽  
Vol 306 (6) ◽  
pp. F579-F587 ◽  
Author(s):  
Jeff L. Zhang ◽  
Glen Morrell ◽  
Henry Rusinek ◽  
Lizette Warner ◽  
Pierre-Hugues Vivier ◽  
...  

Blood oxygen level-dependent (BOLD) MRI data of kidney, while indicative of tissue oxygenation level (Po2), is in fact influenced by multiple confounding factors, such as R2, perfusion, oxygen permeability, and hematocrit. We aim to explore the feasibility of extracting tissue Po2 from renal BOLD data. A method of two steps was proposed: first, a Monte Carlo simulation to estimate blood oxygen saturation (SHb) from BOLD signals, and second, an oxygen transit model to convert SHb to tissue Po2. The proposed method was calibrated and validated with 20 pigs (12 before and after furosemide injection) in which BOLD-derived tissue Po2 was compared with microprobe-measured values. The method was then applied to nine healthy human subjects (age: 25.7 ± 3.0 yr) in whom BOLD was performed before and after furosemide. For the 12 pigs before furosemide injection, the proposed model estimated renal tissue Po2 with errors of 2.3 ± 5.2 mmHg (5.8 ± 13.4%) in cortex and −0.1 ± 4.5 mmHg (1.7 ± 18.1%) in medulla, compared with microprobe measurements. After injection of furosemide, the estimation errors were 6.9 ± 3.9 mmHg (14.2 ± 8.4%) for cortex and 2.6 ± 4.0 mmHg (7.7 ± 11.5%) for medulla. In the human subjects, BOLD-derived medullary Po2 increased from 16.0 ± 4.9 mmHg (SHb: 31 ± 11%) at baseline to 26.2 ± 3.1 mmHg (SHb: 53 ± 6%) at 5 min after furosemide injection, while cortical Po2 did not change significantly at ∼58 mmHg (SHb: 92 ± 1%). Our proposed method, validated with a porcine model, appears promising for estimating tissue Po2 from renal BOLD MRI data in human subjects.


2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 198-198
Author(s):  
Bishoy A. Gayed ◽  
Rami Hallac ◽  
Ramy F. Youssef ◽  
Franto Francis ◽  
Qing Yuan ◽  
...  

198 Background: Tumor hypoxia is associated with worse pathologic features and oncological outcomes. Blood Oxygen Level Dependent (BOLD) MRI evaluates changes in endogenous contrast generated by paramagnetic deoxy-hemoglobin to non-invasively evaluate tissue oxygenation. Prior attempts using carbogen-based (95%O2 + 5%CO2) imaging were limited by patient tolerance. We present the first-in-man evaluation of a novel oxygen breathing challenge technique to monitor tissue oxygenation with BOLD MRI in patients with prostate cancer. Methods: Following IRB approval, 10 patients with clinically localized prostate cancer scheduled for radical prostatectomy underwent preoperative imaging with a 3-Tesla MRI scanner. Images were acquired using a 6-element SENSE body transmit coil and endorectal receive coil. T2* signal intensity is dependent on the concentration of deoxy-hemoglobin. Signal intensity measurements were obtained at different time points. Shorter T2* times imply the presence of hypoxia. Dynamic T2* maps were acquired while subjects breathed air for 2 mins followed by oxygen (15 l/min). Results: 10 patients (median age: 59 years (range 48-73), median PSA 6.9 ng/ml (range 2.5-25), with prostate cancer (Gleason sum 6- 7, 8-9 in 7 and 3 patients respectively) underwent BOLD MRI within 3 weeks of definitive management with a robotic assisted laparoscopic prostatectomy. All patients tolerated BOLD MRI with oxygen challenge without difficulty. Evaluation of BOLD MRI revealed wide variation in T2* values within the prostates from a median of 14.7 ± .71 ms to 44.5 ± 3.3ms. Surrounding muscle T2* values were similar for all patients, indicating that heterogeneous values were specific to each patient’s prostate. Shorter T2* values were seen in Gleason 6-7 than Gleason 8- 9 cancers, indicating more hypoxic areas in these tumors. HIF-1α staining was strongly positive in all tumors. Conclusions: BOLD MRI with oxygen challenge is well tolerated in patients and is a feasible noninvasive technique to study tissue oxygenation in tumors. Differential oxygenation patterns of prostates appear to correlate with pathological features. Further testing is needed to validate these findings.


2015 ◽  
Vol 35 (11) ◽  
pp. 1746-1756 ◽  
Author(s):  
Julien Poublanc ◽  
Adrian P Crawley ◽  
Olivia Sobczyk ◽  
Gaspard Montandon ◽  
Kevin Sam ◽  
...  

We define cerebral vascular reactivity (CVR) as the ratio of the change in blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal (S) to an increase in blood partial pressure of CO2 (PCO2): % Δ S/Δ PCO2 mm Hg. Our aim was to further characterize CVR into dynamic and static components and then study 46 healthy subjects collated into a reference atlas and 20 patients with unilateral carotid artery stenosis. We applied an abrupt boxcar change in PCO2 and monitored S. We convolved the PCO2 with a set of first-order exponential functions whose time constant τ was increased in 2-second intervals between 2 and 100 seconds. The τ corresponding to the best fit between S and the convolved PCO2 was used to score the speed of response. Additionally, the slope of the regression between S and the convolved PCO2 represents the steady-state CVR (ssCVR). We found that both prolongations of τ and reductions in ssCVR (compared with the reference atlas) were associated with the reductions in CVR on the side of the lesion. τ and ssCVR are respectively the dynamic and static components of measured CVR.


2019 ◽  
Vol 53 (2) ◽  
pp. 1801854 ◽  
Author(s):  
Sira Thiel ◽  
Franziska Lettau ◽  
Protazy Rejmer ◽  
Cristina Rossi ◽  
Sarah R. Haile ◽  
...  

Impaired cerebral vascular reactivity (CVR) increases long-term stroke risk. Obstructive sleep apnoea (OSA) is associated with peripheral vascular dysfunction and vascular events. The aim of this trial was to evaluate the effect of continuous positive airway pressure (CPAP) withdrawal on CVR.41 OSA patients (88% male, mean age 57±10 years) were randomised to either subtherapeutic or continuation of therapeutic CPAP. At baseline and after 2 weeks, patients underwent a sleep study and magnetic resonance imaging (MRI). CVR was estimated by quantifying the blood oxygen level-dependent (BOLD) MRI response to breathing stimuli.OSA did recur in the subtherapeutic CPAP group (mean treatment effect apnoea–hypopnoea index +38.0 events·h−1, 95% CI 24.2–52.0; p<0.001) but remained controlled in the therapeutic group. Although there was a significant increase in blood pressure upon CPAP withdrawal (mean treatment effect +9.37 mmHg, 95% CI 1.36–17.39; p=0.023), there was no significant effect of CPAP withdrawal on CVR assessedviaBOLD MRI under either hyperoxic or hypercapnic conditions.Short-term CPAP withdrawal did not result in statistically significant changes in CVR as assessed by functional MRI, despite the recurrence of OSA. We thus conclude that, unlike peripheral endothelial function, CVR is not affected by short-term CPAP withdrawal.


2011 ◽  
Vol 13 (5) ◽  
pp. 370-377 ◽  
Author(s):  
Monika L. Gloviczki ◽  
Lilach O. Lerman ◽  
Stephen C. Textor

Author(s):  
Danielle Jin-Kwang Kim ◽  
Rachel C. Drew ◽  
Christopher T. Sica ◽  
Qing X. Yang ◽  
Amanda J. Miller ◽  
...  

One in three Americans suffer from kidney diseases such as chronic kidney disease, and one of the etiologies is suggested to be the long-term renal hypoxia. Interestingly, sympathetic nervous system activation evokes a renal vasoconstrictor effect that may limit oxygen delivery to the kidney. In this report, we sought to determine if sympathetic activation evoked by lower body negative pressure (LBNP) would decrease cortical and medullary oxygenation in humans. LBNP was activated in a graded fashion (LBNP; -10, -20, and -30 mmHg), as renal oxygenation was measured (T2*, Blood Oxygen Level Dependent, BOLD MRI; n = 8). At a separate time, renal blood flow velocity (RBV) to the kidney was measured (n = 13) as LBNP was instituted. LBNP significantly reduced RBV (P = 0.041) at -30 mmHg of LBNP (Δ-8.17 ± 3.75 cm/s). Moreover, both renal medullary and cortical T2* were reduced with the graded LBNP application (main effect for the level of LBNP P = 0.0008). During recovery, RBV rapidly returned to baseline, whereas medullary T2* remained depressed into the first min of the recovery. In conclusion, sympathetic activation reduces renal blood flow and leads to a significant decrease in oxygenation in the renal cortex and medulla.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1867 ◽  
Author(s):  
Joshua M. Thurman ◽  
Faikah Gueler

Kidney diseases can be caused by a wide range of genetic, hemodynamic, toxic, infectious, and autoimmune factors. The diagnosis of kidney disease usually involves the biochemical analysis of serum and blood, but these tests are often insufficiently sensitive or specific to make a definitive diagnosis. Although radiologic imaging currently has a limited role in the evaluation of most kidney diseases, several new imaging methods hold great promise for improving our ability to non-invasively detect structural, functional, and molecular changes within the kidney. New methods, such as dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and blood oxygen level-dependent (BOLD) MRI, allow functional imaging of the kidney. The use of novel contrast agents, such as microbubbles and nanoparticles, allows the detection of specific molecules in the kidney. These methods could greatly advance our ability to diagnose disease and also to safely monitor patients over time. This could improve the care of individual patients, and it could also facilitate the evaluation of new treatment strategies.


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