The idea that in vivo intravoxel incoherent motion magnetic resonance signal is influenced by blood motion in the microvasculature is exciting, because it suggests that local and quantitative perfusion information can be obtained in a simple and elegant way from a few diffusion-weighted images, without contrast injection. When the method was proposed in the late 1980s some doubts appeared as to its feasibility, and, probably because the signal to noise and image quality at the time was not sufficient, no obvious experimental evidence could be produced to alleviate them. Helped by the tremendous improvements seen in the last three decades in MR hardware, pulse design, and post-processing capabilities, an increasing number of encouraging reports on the value of intravoxel incoherent motion perfusion imaging have emerged. The aim of this article is to review the current published evidence on the feasibility of in vivo perfusion imaging with intravoxel incoherent motion MRI.

Intravoxel incoherent motion MRI as a means to measure in vivo perfusion: A review of the evidence

Radiation necrosis is a serious potential adverse event of stereotactic radiosurgery that cannot be reliably differentiated from recurrent tumor using conventional imaging techniques. Intravoxel incoherent motion (IVIM) is a magnetic resonance imaging (MRI) based method that uses a diffusion-weighted sequence to estimate quantitative perfusion and diffusion parameters. This study evaluated the IVIM-derived apparent diffusion coefficient (ADC) and perfusion fraction (f), and compared the results to the gold standard histopathological-defined outcomes of radiation necrosis or recurrent tumor. Nine patients with ten lesions were included in this study; all lesions exhibited radiographic progression after stereotactic radiosurgery for brain metastases that subsequently underwent surgical resection due to uncertainty regarding the presence of radiation necrosis versus recurrent tumor. Pre-surgical IVIM was performed to obtain f and ADC values and the results were compared to histopathology. Five lesions exhibited pathological radiation necrosis and five had predominantly recurrent tumor. The IVIM perfusion fraction reliably differentiated tumor recurrence from radiation necrosis (fmean = 10.1 ± 0.7 vs. 8.3 ± 1.2, p = 0.02; cutoff value of 9.0 yielding a sensitivity/specificity of 100%/80%) while the ADC did not distinguish between the two (ADCmean = 1.1 ± 0.2 vs. 1.2 ± 0.4, p = 0.6). IVIM shows promise in differentiating recurrent tumor from radiation necrosis for brain metastases treated with radiosurgery, but needs to be validated in a larger cohort.

Differentiating radiation necrosis from tumor progression in brain metastases treated with stereotactic radiotherapy: utility of intravoxel incoherent motion perfusion MRI and correlation with histopathology.

Brain metastases are the most common intracranial tumors and occur in 20-40% of all cancer patients. Lung cancer, breast cancer, and melanoma are the most frequent primary cancers to develop brain metastases. Treatment options include surgical resection, whole brain radiotherapy, stereotactic radiosurgery, and systemic treatment such as targeted or immune therapy. Anatomical magnetic resonance imaging (MRI) of the tumor (in particular post-Gadolinium T1-weighted and T2-weighted FLAIR) provide information about lesion morphology and structure, and are routinely used in clinical practice for both detection and treatment response evaluation for brain metastases. Advanced MRI biomarkers that characterize the cellular, biophysical, micro-structural and metabolic features of tumors have the potential to improve the management of brain metastases from early detection and diagnosis, to evaluating treatment response. Magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), quantitative magnetization transfer (qMT), diffusion-based tissue microstructure imaging, trans-membrane water exchange mapping, and magnetic susceptibility weighted imaging (SWI) are advanced MRI techniques that will be reviewed in this article as they pertain to brain metastases.

/pdf/advanced-magnetic-resonance-imaging-techniques-in-management-37s2eqjfxv.pdf

Advanced Magnetic Resonance Imaging Techniques in Management of Brain Metastases.

Objective Summarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and highlight the latest bench-to-bedside developments. Methods Experts in advanced MRI techniques applied to high-grade glioma treatment response assessment convened through a European framework. Current evidence regarding the potential for monitoring biomarkers in adult high-grade glioma is reviewed, and individual modalities of perfusion, permeability, and microstructure imaging are discussed (in Part 1 of two). In Part 2, we discuss modalities related to metabolism and/or chemical composition, appraise the clinic readiness of the individual modalities, and consider post-processing methodologies involving the combination of MRI approaches (multiparametric imaging) or machine learning (radiomics). Results High-grade glioma vasculature exhibits increased perfusion, blood volume, and permeability compared with normal brain tissue. Measures of cerebral blood volume derived from dynamic susceptibility contrast-enhanced MRI have consistently provided information about brain tumor growth and response to treatment; it is the most clinically validated advanced technique. Clinical studies have proven the potential of dynamic contrast-enhanced MRI for distinguishing post-treatment related effects from recurrence, but the optimal acquisition protocol, mode of analysis, parameter of highest diagnostic value, and optimal cut-off points remain to be established. Arterial spin labeling techniques do not require the injection of a contrast agent, and repeated measurements of cerebral blood flow can be performed. The absence of potential gadolinium deposition effects allows widespread use in pediatric patients and those with impaired renal function. More data are necessary to establish clinical validity as monitoring biomarkers. Diffusion-weighted imaging, apparent diffusion coefficient analysis, diffusion tensor or kurtosis imaging, intravoxel incoherent motion, and other microstructural modeling approaches also allow treatment response assessment; more robust data are required to validate these alone or when applied to post-processing methodologies. Conclusion Considerable progress has been made in the development of these monitoring biomarkers. Many techniques are in their infancy, whereas others have generated a larger body of evidence for clinical application.

/pdf/high-grade-glioma-treatment-response-monitoring-biomarkers-a-gx8cop4c.pdf

High-Grade Glioma Treatment Response Monitoring Biomarkers: A Position Statement on the Evidence Supporting the Use of Advanced MRI Techniques in the Clinic, and the Latest Bench-to-Bedside Developments. Part 1: Perfusion and Diffusion Techniques

The purpose of this article was to show basic principles, acquisition, advantages, disadvantages, and clinical applications of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI). IVIM MRI as a method was introduced in the late 1980s, but recently it started attracting more interest thanks to its applications in many fields, particularly in oncology and neuroradiology. This imaging technique has been developed with the objective of obtaining not only a functional analysis of different organs but also different types of lesions. Among many accessible tools in diagnostic imaging, IVIM MRI aroused the interest of many researchers in terms of studying its applicability in the evaluation of abdominal organs and diseases. The major conclusion of this article is that IVIM MRI seems to be a very auspicious method to investigate the human body, and that nowadays the most promising clinical application for IVIM perfusion MRI is oncology. However, due to lack of standardisation of image acquisition and analysis, further studies are needed to validate this method in clinical practice.

/pdf/intravoxel-incoherent-motion-magnetic-resonance-imaging-119cwpjuls.pdf

Intravoxel incoherent motion magnetic resonance imaging: basic principles and clinical applications.

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 2 ). 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 2 . 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 2 ) 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 R 2 ) 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.

http://www.ajnr.org/content/ajnr/37/12/2251.full.pdf

A Simplified Model for Intravoxel Incoherent Motion Perfusion Imaging of the Brain.

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A Simplified Model for Intravoxel Incoherent Motion Perfusion Imaging of the Brain.