Using magnetic resonance imaging and spectroscopy in cancer diagnostics and monitoring: preclinical and clinical approaches

Abstract

Nuclear Magnetic Resonance (MR) based imaging has become an integrated domain in today's oncology research and clinical management of cancer patients. MR is a unique imaging modality among numerous other imaging modalities by providing access to anatomical, physiological, biochemical and molecular details of tumour with excellent spatial and temporal resolutions. In this review we will cover established and investigational MR imaging (MRI) and MR spectroscopy (MRS) techniques used for cancer imaging and demonstrate wealth of information on tumour biology and clinical applications MR techniques offer for oncology research both in preclinical and clinical settings. Emphasis is given not only to the variety of information which may be obtained but also the complementary nature of the techniques. This ability to determine tumour type, grade, invasiveness, degree of hypoxia, microvacular characteristics, and metabolite phenotype, has already profoundly transformed oncology research and patient management. It is evident from the data reviewed that MR techniques will play a key role in uncovering molecular fingerprints of cancer, developing targeted treatment strategies and assessing responsiveness to treatment for personalized patient management, thereby allowing rapid translation of imaging research conclusions into the benefit of clinical oncology.

Figure 1

Schematic summary of in vivo properties of tumors that are probed by MR techniques.

Figure 2

Axial MR images from a patient with a right thalamic high grade glioma acquired at 1.5T (A) T₁-weighted; (B) T₂-weighted; (C) DWI; (D) fractional anisotropy image (E) ₁H MRS from the tumor core with major peaks assigned as follows: Choline-containing compounds (3.23ppm), total creatine (at 3.03 ppm) and mobile lipids (at 2.0, 1.3 and 0.9 ppm); (F) Choline-containing compounds-to-total creatine (Cho/Cr) ratio image from multivoxel MRS represented as a color map on a T₁-weighted image acquired after injection of a Gd-contrast agent.

Figure 3

A BT4C rat glioma imaged at 4.7 T using Carr-Purcell (CP) multi-echo MRI. A BT4C glioma bearing rat was treated with herpes simplex virus thymidine kinase-ganciclovir gene therapy. (A) Shows a CP MR image acquired with short and panel (B) with long interpulse interval. Panel (C) is a normalized difference image of images shown in panels (A) and (B) yielding the so-called dynamic dephasing contrast. It should be noted that in this image (C) free water gives no signal and thus both ventricles and a tumor cyst appear dark. Instead, the tumor tissue undergoing cytotoxic cell death shows bright signal that is not obvious from either of the images in (A) and (B). Courtesy of Dr. Olli H.J. Grohn, University of Eastern Finland, Kuopio, Finland.

Figure 4

Postcontrast image (T_1C), endothelial transfer constant (K_trans), extracellular extravascular space (v_e) and blood plasma volume (v_p) maps obtained using DCE MRI in a patient with a glioblastoma multiforme. Courtesy of Drs. Geoffrey Parker and Samantha Mills, University of Manchester, UK.

Figure 5

Transverse T₁ maps of drug-treated and untreated EL-4 tumors in animals injected with PS-active (GST-C2A-Gd) and PS-inactive (GST-C2A-Gd) contrast agents. Color scale indicates T₁ values for image voxels. In this example, contrast agents were matched for relaxation rate. Images were acquired immediately before injection of contrast agent (a T₁ map acquired from a tumor before injection is shown on the left-hand side) and at 24 h after injection. Reference capillary was placed adjacent to the tumors, which were implanted on lower areas of backs of animals. Position of the tumor is indicated on the gray-scale image. (A) Etoposide+cyclophoshamide-treated tumor in animal injected with PS-active GST-C2A-Gd (TA). (B) Drug combination-treated tumor in animal injected with PS-inactive GST-C2A-Gd (TI). (C) Untreated tumor in animal injected with PS-active GSTC2A-Gd (UA). (D) Untreated tumor in animal injected with PS-inactive GST-C2A-Gd (UI). Drug combination-treated tumor in an animal injected with PS-active contrast agent shows greater accumulation at 24 h after injection (A). Courtesy of Dr. Kevin Brindle, University of Cambridge, UK.