Charles H. Cunningham

Bio: Charles H. Cunningham is an academic researcher from Sunnybrook Research Institute. The author has contributed to research in topics: Magnetic resonance spectroscopic imaging & Pulse sequence. The author has an hindex of 31, co-authored 90 publications receiving 5303 citations. Previous affiliations of Charles H. Cunningham include Women's College, Kolkata & University of Toronto.

Hyperpolarized 13C Lactate, Pyruvate, and Alanine: Noninvasive Biomarkers for Prostate Cancer Detection and Grading

Abstract: An extraordinary new technique using hyperpolarized (13)C-labeled pyruvate and taking advantage of increased glycolysis in cancer has the potential to improve the way magnetic resonance imaging is used for detection and characterization of prostate cancer The aim of this study was to quantify, for the first time, differences in hyperpolarized [1-(13)C] pyruvate and its metabolic products between the various histologic grades of prostate cancer using the transgenic adenocarcinoma of mouse prostate (TRAMP) model Fast spectroscopic imaging techniques were used to image lactate, alanine, and total hyperpolarized carbon (THC = lactate + pyruvate + alanine) from the entire abdomen of normal mice and TRAMP mice with low- and high-grade prostate tumors in 14 s Within 1 week, the mice were dissected and the tumors were histologically analyzed Hyperpolarized lactate SNR levels significantly increased (P < 005) with cancer development and progression (41 +/- 11, 74 +/- 17, and 154 +/- 24 in normal prostates, low-grade primary tumors, and high-grade primary tumors, respectively) and had a correlation coefficient of 095 with the histologic grade In addition, there was minimal overlap in the lactate levels between the three groups with only one of the seven normal prostates overlapping with the low-grade primary tumors The amount of THC, a possible measure of substrate uptake, and hyperpolarized alanine also increased with tumor grade but showed more overlap between the groups In summary, elevated hyperpolarized lactate and potentially THC and alanine are noninvasive biomarkers of prostate cancer presence and histologic grade that could be used in future three-dimensional (13)C spectroscopic imaging studies of prostate cancer patients

Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles

Abstract: Contrast agents incorporating superparamagnetic iron-oxide nanoparticles have shown promise as a means to visualize labeled cells using MRI. Labeled cells cause significant signal dephasing due to the magnetic field inhomogeneity induced in water molecules near the cell. With the resulting signal void as the means for detection, the particles behave as a negative contrast agent, which can suffer from partial-volume effects. In this paper, a new method is described for imaging labeled cells with positive contrast. Spectrally selective RF pulses are used to excite and refocus the off-resonance water surrounding the labeled cells so that only the fluid and tissue immediately adjacent to the labeled cells are visible in the image. Phantom, in vitro, and in vivo experiments show the feasibility of the new method. A significant linear correlation (r = 0.87, P < 0.005) between the estimated number of cells and the signal was observed.

Saturated double-angle method for rapid B1+ mapping.

Abstract: For in vivo magnetic resonance imaging at high field (> or =3 T) it is essential to consider the homogeneity of the active B(1) field (B(1)+), particularly if surface coils are used for RF transmission. A new method is presented for highly rapid B(1)+ magnitude mapping. It combines the double angle method with a B(1)-insensitive magnetization-reset sequence such that the choice of repetition time (TR) is independent of T(1) and with a multislice segmented (spiral) acquisition to achieve volumetric coverage with adequate spatial resolution in a few seconds. Phantom experiments confirmed the accuracy of this technique even when TR << T(1), with the side effect being lowered SNR. The speed of this method enabled B(1)+ mapping in the chest and abdomen within a single breath-hold. In human cardiac imaging, the method enabled whole-heart coverage within a single 16-s breath-hold. Results from phantoms and healthy volunteers at 1.5 T and 3 T are presented.

Sparse MRI: The application of compressed sensing for rapid MR imaging.

Abstract: The sparsity which is implicit in MR images is exploited to significantly undersample k -space. Some MR images such as angiograms are already sparse in the pixel representation; other, more complicated images have a sparse representation in some transform domain–for example, in terms of spatial finite-differences or their wavelet coefficients. According to the recently developed mathematical theory of compressedsensing, images with a sparse representation can be recovered from randomly undersampled k -space data, provided an appropriate nonlinear recovery scheme is used. Intuitively, artifacts due to random undersampling add as noise-like interference. In the sparse transform domain the significant coefficients stand out above the interference. A nonlinear thresholding scheme can recover the sparse coefficients, effectively recovering the image itself. In this article, practical incoherent undersampling schemes are developed and analyzed by means of their aliasing interference. Incoherence is introduced by pseudo-random variable-density undersampling of phase-encodes. The reconstruction is performed by minimizing the 1 norm of a transformed image, subject to data

Compressed Sensing MRI

Abstract: This article reviews the requirements for successful compressed sensing (CS), describes their natural fit to MRI, and gives examples of four interesting applications of CS in MRI. The authors emphasize on an intuitive understanding of CS by describing the CS reconstruction as a process of interference cancellation. There is also an emphasis on the understanding of the driving factors in applications, including limitations imposed by MRI hardware, by the characteristics of different types of images, and by clinical concerns.

Metabolic Imaging of Patients with Prostate Cancer Using Hyperpolarized [1-13C]Pyruvate

Abstract: This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-13C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo 13C MR data, it is possible to evaluate the distribution of agents such as [1-13C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds. Preclinical studies in cancer models have detected elevated levels of hyperpolarized [1-13C]lactate in tumor, with the ratio of [1-13C]lactate/[1-13C]pyruvate being increased in high-grade tumors and decreased after successful treatment. Translation of this technology into humans was achieved by modifying the instrument that generates the hyperpolarized agent, constructing specialized radio frequency coils to detect 13C nuclei, and developing new pulse sequences to efficiently capture the signal. The study population comprised patients with biopsy-proven prostate cancer, with 31 subjects being injected with hyperpolarized [1-13C]pyruvate. The median time to deliver the agent was 66 s, and uptake was observed about 20 s after injection. No dose-limiting toxicities were observed, and the highest dose (0.43 ml/kg of 230 mM agent) gave the best signal-to-noise ratio for hyperpolarized [1-13C]pyruvate. The results were extremely promising in not only confirming the safety of the agent but also showing elevated [1-13C]lactate/[1-13C]pyruvate in regions of biopsy-proven cancer. These findings will be valuable for noninvasive cancer diagnosis and treatment monitoring in future clinical trials.