Mary Anne McLean

A comparison of quantitative methods for clinical imaging with hyperpolarized 13C-pyruvate

Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized 13C‐labelled molecules, such as the conversion of [1‐13C]pyruvate to [1‐13C]lactate, to be dynamically and non‐invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model‐free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two‐way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time‐to‐peak and the lactate‐to‐pyruvate area under the curve ratio were simple model‐free approaches that accurately represented the full reaction, with the time‐to‐peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized 13C data.

Multi‐institutional validation of a novel textural analysis tool for preoperative stratification of suspected thyroid tumors on diffusion‐weighted MRI

Ultrasound‐guided fine needle aspirate cytology fails to diagnose many malignant thyroid nodules; consequently, patients may undergo diagnostic lobectomy. This study assessed whether textural analysis (TA) could noninvasively stratify thyroid nodules accurately using diffusion‐weighted MRI (DW‐MRI).

Multimodal MRI can identify perfusion and metabolic changes in the invasive margin of glioblastomas

To use perfusion and magnetic resonance (MR) spectroscopy to compare the diffusion tensor imaging (DTI)‐defined invasive and noninvasive regions. Invasion of normal brain is a cardinal feature of glioblastomas (GBM) and a major cause of treatment failure. DTI can identify invasive regions.

Slice-selective broadband refocusing pulses for the robust generation of crushed spin-echoes

A major challenge for in vivo magnetic resonance spectroscopy with point-resolved spectroscopy (PRESS) is the low signal intensity for the measurement of weakly scalar coupled spins, for example lactate. The chemical-shift displacement error between the two coupling partners of the lactate molecule leads to a signal decrease. The chemical-shift displacement error is decreased and therefore the lactate signal is increased by using refocusing pulses with a broad bandwidth. Previously, slice-selective broadband universal rotation pulses (S-BURBOP) were designed and applied as refocusing pulses in the PRESS pulse sequence (Janich MA, et al., Journal of Magnetic Resonance, 2011, 213, 126-135). However, S-BURBOP pulses leave a phase error across the slice which is superimposed on the spectra when spatially resolving the PRESS voxel. In the present novel design of slice-selective broadband refocusing pulses (S-BREBOP) this phase error is avoided. S-BREBOP pulses obtain 2.5 times the bandwidth of conventional Shinnar-Le Roux pulses and are robust against ±20% miscalibration of the B(1) amplitude. S-BREBOP pulses were validated in phantoms and in a low-grade brain tumor of a patient. Compared to conventional Shinnar-Le Roux pulses they lead to a decrease of the chemical-shift displacement error and consequently a lactate signal increase.

Hyperpolarized carbon-13 magnetic resonance spectroscopic imaging: a clinical tool for studying tumour metabolism

Glucose metabolism in tumours is reprogrammed away from oxidative metabolism, even in the presence of oxygen. Non-invasive imaging techniques can probe these alterations in cancer metabolism providing tools to detect tumours and their response to therapy. Although Positron Emission Tomography with (18F)2-fluoro-2-deoxy-D-glucose (18F-FDG PET) is an established clinical tool to probe cancer metabolism, it has poor spatial resolution and soft tissue contrast, utilizes ionizing radiation and only probes glucose uptake and phosphorylation and not further downstream metabolism. Magnetic Resonance Spectroscopy (MRS) has the capability to non-invasively detect and distinguish molecules within tissue but has low sensitivity and can only detect selected nuclei. Dynamic Nuclear Polarization (DNP) is a technique which greatly increases the signal-to-noise ratio (SNR) achieved with MR by significantly increasing nuclear spin polarization and this method has now been translated into human imaging. This review provides a brief overview of this process, also termed Hyperpolarized Carbon-13 Magnetic Resonance Spectroscopic Imaging (HP 13C-MRSI), its applications in preclinical imaging, an outline of the current human trials that are ongoing, as well as future potential applications in oncology.

PET-guided MR Spectroscopy in Alzheimer’s disease

To determine whether the level of metabolites in magnetic resonance spectroscopy (MRS) is a representative marker of underlying pathological changes identified in positron emission tomographic (PET) images in Alzheimer disease (AD).

Quantitative and textural analysis of magnetization transfer and diffusion images in the early detection of brain metastases

The sensitivity of the magnetization transfer ratio (MTR) and apparent diffusion coefficient (ADC) for early detection of brain metastases was investigated in mice and humans.

Detecting gas-induced vasomotor changes via blood oxygenation level-dependent contrast in healthy breast parenchyma and breast carcinoma

To evaluate blood oxygenation level‐dependent (BOLD) contrast changes in healthy breast parenchyma and breast carcinoma during administration of vasoactive gas stimuli.

Imaging intralesional heterogeneity of sodium concentration in multiple sclerosis: Initial evidence from 23 Na-MRI

Sodium MRI (23Na-MRI) has been used to non-invasively quantify tissue sodium but has been limited by low spatial resolution. Here we demonstrate for the first time that high resolution 23Na-MRI reveals the spatial heterogeneity of sodium concentration within a multiple sclerosis (MS) lesion. A patient with treatment-naïve relapsing-remitting MS and a ring-enhancing lesion was imaged using 23Na-MRI. The periphery of the lesion demonstrated an elevated total sodium content compared to the normal appearing white and grey matter (p < 0.01), as well as a heterogeneous distribution of both the total tissue sodium concentration and the intracellular-weighted sodium concentration.

Multi-Parametric and Multi-Regional Histogram Analysis of MRI: Revealing Imaging Phenotypes of Glioblastoma Correlated with Patient Survival

Introduction Glioblastoma is characterized by its remarkable heterogeneity and dismal prognosis. Histogram analysis of quantitative magnetic resonance imaging (MRI) is an important in vivo method to study intratumoral heterogeneity. With large amounts of histogram features generated, integrating these modalities effectively for clinical decision remains a challenge. Methods A total of 80 patients with supratentorial primary glioblastoma were recruited. All patients received surgery and standard regimen of temozolomide chemoradiotherapy. Diagnosis was confirmed by pathology. Anatomical T2-weighted, T1-weighted post-contrast and FLAIR images, as well as dynamic susceptibility contrast (DSC), diffusion tensor imaging (DTI) and chemical shift imaging were acquired preoperatively using a 3T MRI scanner. DTI-p, DTI-q, relative cerebral blood volume (rCBV), mean transit time (MTT) and relative cerebral blood flow (rCBF) maps were generated. Contrast-enhancing (CE) and non-enhancing (NE) regions of interest were manually delineated. Voxel intensity histograms were constructed from the CE and NE regions independently. Patient clustering was performed by the Multi-View Biological Data Analysis (MVDA) approach. Kaplan-Meier and Cox proportional hazards regression analyses were performed to evaluate the relevance of the patient clustering to survival. The histogram features selected from MVDA approach were evaluated using receiver operator characteristics (ROC) curve analysis. The metabolic signatures of the patient clusters were analyzed by multivoxel MR spectroscopy (MRS). Results The MVDA approach yielded two final patient clusters, consisting of 53 and 27 patients respectively. The two patient subgroups showed significance for overall survival (p = 0.007, HR = 0.32) and progression-free survival (p < 0.001, HR = 0.33) in multivariate Cox regression analysis. Among the features selected by MVDA, higher mean value of DTI-q in the non-enhancing region contributed to a worse OS (HR = 1.40, p = 0.020) and worse PFS (HR = 1.36, p = 0.031). Multivoxel MRS showed N-acetylaspartate/creatine (NAA/Cr) ratio between the two clusters, both in the CE region (p < 0.001) and NE region (p = 0.013). Glutamate/Cr (Glu/Cr) ratio and glutamate + glutamine/Cr (Glx/Cr) of the cluster 1 was significantly lower than cluster 2 (p = 0.037, and 0.027 respectively) In the NE region. Discussion This study demonstrated that integrating multi-parametric and multi-regional MRI histogram features may help to stratify patients. The histogram features selected from the proposed approach may be used as potential imaging markers in personalized treatment strategy and response determination.