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Blood Oxygenation Level-Dependent Magnetic Resonance Imaging

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Blood Oxygenation Level-Dependent Magnetic Resonance Imaging Journal name: OncoTargets and Therapy Article Designation: Original Research Year: 2016 Volume: 9 OncoTargets and Therapy Dovepress Running head verso: Di et al Running head recto: BOLD MRI during carbogen breathing open access to scientific and medical research DOI: http://dx.doi.org/10.2147/OTT.S105480 Open Access Full Text Article ORIGINAL RESEARCH Blood oxygenation level-dependent magnetic resonance imaging during carbogen breathing: differentiation between prostate cancer and benign prostate hyperplasia and correlation with vessel maturity Ningning Di,1,2,* Ning Objective: The aim of this study was to investigate whether the blood oxygenation level- Mao,3,* Wenna Cheng,4 dependent (BOLD) contrast magnetic resonance imaging (MRI) can evaluate tumor maturity and Haopeng Pang,1 Yan Ren,1 preoperatively differentiate prostate cancer (PCa) from benign prostate hyperplasia (BPH). Ning Wang,2 Xinjiang Liu,2 Patients and methods: BOLD MRI based on transverse relaxation time*-weighted echo planar imaging was performed to assess PCa (19) and BPH (22) responses to carbogen (95% O and Bin Wang5 2 5% CO2). The average signal values of PCa and BPH before and after carbogen breathing and 1Department of Radiology, Affiliated the relative increased signal values were computed, respectively. The endothelial-cell marker, Huashan Hospital of Fudan University, Shanghai, 2Department of Radiology, CD31, and the pericyte marker, α-smooth muscle actin (mature vessels), were detected with Binzhou Medical University Affiliated immunofluorescence, and were assessed by microvessel density (MVD) and microvessel peri- Hospital, Binzhou, 3Department of Radiology, Yantai Yuhangding Hospital, cyte density (MPD). The microvessel pericyte coverage index (MPI) was used to evaluate the Yantai, 4Department of Pharmacy, degree of vascular maturity. The changed signal from BOLD MRI was correlated with MVD, Binzhou Medical University Affiliated MPD, and MPI. Hospital, Binzhou, 5Department of Medical Imaging and Nuclear Results: After inhaling carbogen, both PCa and BPH showed an increased signal, but a lower Medicine, Binzhou Medical University, slope was found in PCa than that in BPH (P,0.05). PCa had a higher MPD and MVD but a lower Yantai, People’s Republic of China MPI than BPH. The increased signal intensity was positively correlated with MPI in PCa and *These authors contributed equally that in BPH (r=0.616, P=0.011; r=0.658, P=0.002); however, there was no correlation between to this work the increased signal intensity and MPD or MVD in PCa than that in BPH (P.0.05). Conclusion: Our results confirmed that the increased signal values induced by BOLD MRI well differentiated PCa from BPH and had a positive correlation with vessel maturity in both Correspondence: Bin Wang Department of Medical Imaging and of them. BOLD MRI can be utilized as a surrogate marker for the noninvasive assessment of Nuclear Medicine, Binzhou Medical the degree of vessel maturity. University, 346 Guanhai Road, BOLD, magnetic resonance imaging, prostate carcinoma, benign prostate Laishan District, Yantai 264000, Keywords: People’s Republic of China hyperplasia, vessel maturity Tel +86 131 6297 1223 Fax +86 53 5691 3002 Email [email protected] Introduction Xinjiang Liu Prostate cancer (PCa) presents a global public health dilemma with increasing incidence Department of Radiology, Binzhou and mortality. In 2002, ∼679,000 men were diagnosed with PCa, and 221,000 patients Medical University Affiliated died from this disease worldwide.1 Tumor angiogenesis characterized by immature Hospital, 522 Huanghe Three Road, Bincheng District, Binzhou 256600, blood vessels is one of the hallmarks of PCa development; thus, targeting tumor vas- People’s Republic of China culature by “starving a tumor to death” was conceived over 4 decades ago and has led Tel +86 133 5628 6368 Email [email protected] to the development of antiangiogenic drugs approved for use against various human submit your manuscript | www.dovepress.com OncoTargets and Therapy 2016:9 4143–4150 4143 Dovepress © 2016 Di et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you http://dx.doi.org/10.2147/OTT.S105480 hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Di et al Dovepress malignancies.2 However, the rigorous depletion of tumor prostate hyperplasia (BPH), few studies have correlated the vessels leads to hypoxia, thereby promoting neovascular- BOLD contrast with intrinsic pathology in PCa and BPH. ization and tumor regrowth. Thus, tumor vessels should not In theory, PCa is featured by immature vessels, whereas cause harm, particularly for mature vessels in the tumor.3 BPH is characterized by mature vessels. Accordingly, we A detailed analysis demonstrated that mature vessels aid in hypothesize that PCa will exhibit a lower increase in sig- tumor treatment because of their roles in improving drug nal in BOLD MRI than BPH. The current study examined delivery,4 increasing oxygenation of potentially sensitized whether BOLD MRI can noninvasively differentiate PCa tumor cells to the cytotoxic actions of chemoradiation,5,6 and from BPH and evaluated the vessel maturity of PCa and BPH enhancing native antitumor immune responses,7,8 suggesting by analyzing the correlation between the changed signal and that the evaluation of tumor vessel maturity in PCa is critical fluorescent staining results. to antiangiogenic treatment and follow-up effectiveness. Although biopsy is the standard diagnostic method to Patients and methods assess vessel maturity, it is not suitable for dynamic monitoring Patients because of its invasive nature and the limited location without A prospective clinical study was conducted in 23 patients with depicting the whole tumor. Thus, a noninvasive method must PCa aged 51–82 years (mean age, 63 years) and 25 patients be developed. Functional magnetic resonance imaging (MRI) with BPH aged 48–73 years (mean age, 60 years). Their is a powerful technique with high spectral and spatial resolu- pathologies were proved by two pathologists, who have tion, which enables the noninvasive imaging of the anatomy worked at least 10 years in the pathology department. Pro- and function in vivo to understand the physiological processes tocols and informed consent provisions were reviewed and better without using ionizing radiation and radioactive trac- approved by the Shandong Medical Imaging Institutional ers. Clinically, combining dynamic contrast enhancement Review Board. All patients provided written informed (Ktrans) and dynamic susceptibility contrast (relative cerebral consent. All patients who did not receive any prior treat- blood volume [rCBV]/relative cerebral blood flow [rCBF]) ment underwent conventional MRI and BOLD MRI before MRI can be a “vascular normalization index” to assess the diagnostic prostate biopsy. Histological identification was vessel maturity in tumor,9 but the MRI perfusion methods obtained from ultrasound-guided core biopsy in 32 patients need contrast agents by intravenous injection, which was not and radical prostatectomy in 16 patients. The medium time suitable for the patients with renal failure. interval between histological results and MRI examination As one functional MRI technique, blood oxygenation was 12 days (ranging 7–53 days). The time interval between level-dependent (BOLD) MRI utilizes the paramagnetic the date of prostate-specific antigen (PSA) measurement properties of deoxyhemoglobin as an intrinsic contrast agent before MRI and the MRI examination ranged from 4 days to affect the transverse relaxation time (T2) independently to 17 days (median =7 days). without giving an additional contrast agent.10 In BOLD MRI, the signal is low in T2* prior to carbogen inhalation, but the Magnetic resonance imaging signal will increase after the patient inhales carbogen, which MRI was performed in the supine position by using a depends on the decreased concentration of deoxyhemoglobin. 3.0 T superconducting magnetic scanner (GE Healthcare Mature vessels always expand after carbogen is inhaled, Bio-Sciences Corp., Piscataway, NJ, USA) equipped with abdo- resulting in increased blood flow and reduced deoxyhemo- men phased-array coils and endorectal coils. The conventional globin, thus elevating the signal. However, immature vessels MRI protocol is composed of fast spin echo axial T2-weighted always exhibit slight dilation and even distribute carried images (repetition time [TR]/echo time [TE] 7,000/120 ms, blood into adjacent tissues; this phenomenon is called the field of view 20×20 cm, matrix 256×512, four excitations, and steal effect.11 Thus, the functional MRI approach can reflect 3 mm slice thickness with 0.6 mm slice gap) and T1-weighted vascular maturity by the altered signal in T2* because of spin echo MRI images in the axial plane (TR/TE 650/8.3 ms, the varying reactivity of vessels to carbogen and has been field of view 20×20 cm, matrix 224×512, four excitations, verified to evaluate the in vivo imaging of tumor vessel matu- and 3 mm slice thickness with 0.6 mm slice
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