ADULT BRAIN A SimplifiedModel for Intravoxel IncoherentMotion Perfusion Imaging of the Brain

BACKGROUND AND PURPOSE: Despite a recent resurgence, intravoxel incoherent motion MRI faces practical challenges, including limited SNR and demanding acquisition and postprocessing requirements. A simplified approach using linear fitting of a subset of higher b-values has seen success in other organ systems. We sought to validate this method for evaluation of brain pathology by comparing perfusion measurements using simplified linear fitting to conventional biexponential fitting. MATERIALS AND METHODS: Forty-nine patients with gliomas and 17 with acute strokes underwent 3T MRI, including DWI with 16 b-values (range, 0 –900 s/mm). Conventional intravoxel incoherent motion was performed using nonlinear fitting of the standard biexponential equation. Simplified intravoxel incoherent motion was performed using linear fitting of the log-normalized signal curves for subsets of b-values 200 s/mm. Comparisons between ROIs (tumors, strokes, contralateral brain) and between models (biexponential and simplified linear) were performed by using 2-way ANOVA. The root mean square error and coefficient of determination (R) were computed for the simplified model, with biexponential fitting as the reference standard. RESULTS: Perfusion maps using simplified linear fitting were qualitatively similar to conventional biexponential fitting. The perfusion fraction was elevated in high-grade (n 33) compared to low-grade (n 16) gliomas and was reduced in strokes compared to the contralateral brain (P .001 for both main effects). Decreasing the number of b-values used for linear fitting resulted in reduced accuracy (higher root mean square error and lower R) compared with full biexponential fitting. CONCLUSIONS: Intravoxel incoherent motion perfusion imaging of common brain pathology can be performed by using simplified linear fitting, with preservation of clinically relevant perfusion information. ABBREVIATIONS: D diffusion coefficient; D pseudo-diffusion coefficient; f perfusion fraction; IVIM intravoxel incoherent motion; rCBV relative cerebral blood volume Initially proposed by Le Bihan et al in the 1980s, the intravoxel incoherent motion (IVIM) model enables simultaneous evaluation of diffusion and perfusion through a multi-b-value diffusion-weighted MRI acquisition. This approach offers theoretical advantages over other perfusion imaging strategies; namely, it is inherently quantitative, provides intrinsic coregistration between perfusion and diffusion parameters, and does not rely on intravenous contrast injection or estimation of an arterial input function. While early investigations were hampered by various technical limitations, advances in field strength, gradient hardware, and echo-planar and parallel imaging technology have led to a resurgent interest in IVIM for a wide range of clinical applications. Brain imaging with IVIM is particularly challenging due to the low blood volume fractions of cerebral tissues and CSF partial volume contamination. Nonetheless, IVIM has now been validated for quantitative evaluation of brain perfusion using clinically available hardware and pulse sequences. Recent work in neuro-oncology has shown the potential for IVIM in differentiating tumor recurrence from posttreatment effects, in the preoperative evaluation of tumor grade, and in differentiating primary CNS lymphoma from glioblastoma. IVIM has also been applied in the setting of acute stroke, where Received January 14, 2016; accepted after revision July 16. From the Department of Medical Imaging (J.C., C.H.), Sunnybrook Health Sciences Centre and University of Toronto, Toronto, Ontario, Canada; Department of Diagnostic and Interventional Radiology (M.R., M.C., C.F.), Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Department of Radiology (M.W.), University of Virginia, Charlottesville, Virginia; and Department of Radiology (M.W., C.F.), Stanford University, Stanford, California. C. Federau received support from the Swiss National Science Foundation. Related abstract previously presented at: Annual Meeting of the American Society of Neuroradiology and the Foundation of the ASNR Symposium, May 21–26, 2016, Washington, DC. Please address correspondence to Christian Federau, MD, MSc, Department of Radiology, Division of Neuroradiology, Stanford University, 300 Pasteur Dr, Stanford, CA 94305-5105; e-mail christian.federau@gmail.com Indicates open access to non-subscribers at www.ajnr. org http://dx.doi. org/10.3174/ajnr.A4929 AJNR Am J Neuroradiol ●:● ● 2016 www.ajnr. org 1 Published September 8, 2016 as 10.3174/ajnr.A4929 Copyright 2016 by American Society of Neuroradiology. perfusion imaging without gadolinium is of particular interest given the association between cerebrovascular disease and renal insufficiency. Despite these promising advancements, practical issues such as low SNR and demanding acquisition and postprocessing requirements may impede more widespread adoption of IVIM in clinical and research settings. Conventional IVIM requires acquisition of a large number of b-values (from 10 to 36), including low b-values sensitive to microcirculatory blood flow (ie, pseudodiffusion) and high b-values in the regime where true molecular diffusion dominates. A biexponential fit is then performed over the full range of b-values using a nonlinear fitting procedure. In contrast, an alternate solution to the IVIM equation can be obtained by performing a linear fit of the log-transformed data, using only a subset of higher b-values. This simplified procedure, also referred to as asymptotic fitting, offers potential advantages over biexponential fitting, including shorter acquisition protocols, computational simplicity, and reduced uncertainty in the setting of low SNR. In principle, this method allows estimation of IVIM parameters using as few as 2 nonzero bvalues. Linear fitting has been applied for imaging of the liver, kidneys, pancreas, prostate, and breast, and in the evaluation of head and neck malignancies. To our knowledge, there has been no systematic comparison of simplified linear fitting with standard biexponential fitting for the evaluation of brain pathology. Therefore, the purpose of this study was: 1) to compare the perfusion fraction (f) estimates obtained using simplified linear fitting with those of conventional biexponential fitting, and 2) to examine the effect of reducing the number of b-values on the quality of the resulting perfusion maps. We performed this analysis in 2 common clinical scenarios, namely, evaluation of brain gliomas and acute strokes. MATERIALS AND METHODS Subjects Subjects were participants in a study of IVIM for the evaluation of brain gliomas at the University of Lausanne from May 2011 to July 2014 and a bicentric study of IVIM for evaluation of acute stroke at the University of Lausanne and the University of Virginia from February 2011 to August 2013. Institutional ethics review board approval at both institutions was obtained, and patient consent was waived. This retrospective analysis includes subject overlap with 2 previously published studies, which applied conventional IVIM methodology for the evaluation of gliomas and strokes, respectively. Inclusion criteria for patients with gliomas were: 1) preoperative imaging, including 16 b-value IVIM acquisition, without corruption by motion artifacts; 2) no relevant treatment history at the time of imaging, including chemotherapy, radiation therapy, or antiangiogenic therapy; and 3) histopathologic tumor diagnosis and grading according to the World Health Organization criteria. Due to the relatively low number of patients with histopathologically confirmed low-grade gliomas (n 10), 6 additional patients with diagnosis of low-grade glioma on radiologic criteria alone were included in the analysis. Inclusion criteria for patients with stroke were: 1) MRI within 5 days of symptom onset, including successful 16-bvalue IVIM acquisition, without corruption by motion artifacts; 2) supratentorial diffusion-restricting infarct of 0.5 cm in minimal diameter; and 3) no hemorrhagic transformation at the time of imaging. MRI Acquisition All imaging was performed on 3T MRI systems (Magnetom Skyra, Verio, or Trio; Siemens, Erlangen, Germany) using 32channel phased array receiver coils. The IVIM acquisition consisted of a Stejskal-Tanner diffusion-weighted EPI spin-echo pulse sequence, with diffusion-weighting obtained along 3 orthogonal directions using 16 different b-values (b 0, 10, 20, 40, 80, 110, 140, 170, 200, 300, 400, 500, 600, 700, 800, 900 s/mm). Images were acquired in the axial plane, with nominal in-plane resolution 1.2 1.2 mm, section thickness 4 mm, NEX 1, acceleration factor 2, bandwidth 1086 –1106 Hz/pixel, TR 4000 ms, TE lowest achievable for each scanner (89 –102 ms). For patients with tumors, DSC perfusion MRI was performed using a T2*-weighted gradient-echo EPI pulse sequence (nominal in-plane resolution 1.8 1.8 mm, section thickness 6 mm, TR 1950 ms, TE 43 ms) sequentially acquired after IV injection of gadoterate meglumine (Dotarem; Guerbet, Aulnay-sous-Bois, France) with a dose of 0.2 mL/kg and a rate of 3 mL/s. Additional conventional images were obtained according to the institutional brain tumor and stroke imaging