Magnetic Resonance Measurement of Breast Tissue Perfusion

Institution: University of California, Davis
Investigator(s): Michael Buonocore, M.D., Ph.D. -
Award Cycle: 1995 (Cycle I) Grant #: 1IB-0156 Award: $48,560
Award Type: IDEA
Research Priorities
Detection, Prognosis and Treatment>Imaging, Biomarkers, and Molecular Pathology: improving detection and diagnosis

Initial Award Abstract (1995)
Early detection of malignant (cancerous) tumors and discrimination from benign (non-cancerous) tumors can reduce human and economic costs by reducing the number of missed malignant breast tumors and reducing the number of biopsies performed on benign tumors. The specific aim of the project is to develop and test a new noninvasive Magnetic Resonance Imaging (MRI) technique for measurement of blood flow through breast tumors. MRI (a technique based on the interaction of hydrogen protons with magnetic fields) has been proposed as a screening tool and our technique would make such screening more specific for malignant tumors. Our hypothesis is that malignant tumors can be distinguished from benign tumors by measurement of the higher blood flow through the malignant tumors. We plan to establish a definitive diagnosis via tissue biopsy which will be made in all subjects and will establish the technique's potential for early detection and diagnosis of malignant tumors.

Blood flow through tissue is referred to as tissue perfusion and measured in milliliters per minute per gram of tissue. The proposed MRI technique is referred to as arterial spin-tagging, first reported in 1992 for brain tissue perfusion. In this technique, flowing blood, prior to entering the tumor, is magnetically labeled and observed by imaging within the tumor. Greater flow into the tumor causes greater image intensity changes compared to images obtained without magnetic labeling. Enhanced angiogenesis (growth of blood vessels) of malignant tumors is the reason for the increased flow, and appears to be a reliable discriminator of benign versus malignant tissue. Arterial spin tagging techniques will show MRI signal enhancement in malignant tumors similar to that shown in dynamic contrast-enhanced MRI, in which signal enhancement results from passage and accumulation of contrast material. Arterial spin-tagging offers greater sensitivity and higher reliability because it can be applied repeatedly to systematically investigate the tissue parameters. It is not limited to observations over a single pass.

The technique may also reduce the incidence of false-negative diagnoses by revealing high tissue blood flow in small tumors that are not observable with standard MRI or other modalities. The technique may have an important role in detection of small tumors at multiple distinct locations that change management. In larger tumors, this technique may be useful to reveal optimal biopsy sites, which will reduce the number of false-negative biopsies and the total number of negative biopsies.

Final Report (1997)
The goal of this project is to develop and test new methods, using magnetic resonance (MR) imaging, for measuring the blood flow through breast tumors, to help determine the presence of abnormal tissue, and to help assess whether the abnormal tissue is malignant or benign (cancerous or non-cancerous). Previous MR studies, using injections of a contrast material (i.e., a drug-like compound that is absorbed by the body’s tissues) to improve the ability to see abnormalities, have shown that the blood flow in malignant tumors is higher than that in benign tumors and normal tissue. Using the new methods, we performed the same type of measurement without the use of an injection of contrast material.

The new MR imaging methods are based on the ability to selectively energize or "tag" the hydrogen of the water in the blood within the very small blood vessels entering the region of suspected abnormal breast tissue. Using these methods, the brightness of the resulting MR image, at each point in the image, depends upon the amount of blood entering the tissue at that point. Both breasts can be examined entirely using these methods in about 30 minutes. To date, these measurements have been obtained in eight normal subjects without breast lesions and five subjects with palpable and/or mammographically visible breast lesions. We have shown that this method is reproducible and extremely sensitive to the amount of blood flowing through breast tissue, and is able to detect small differences that exist between abnormal and normal tissue.

The MRI methods that rely on an injection of contrast material are capable of showing the difference between malignant and benign breast tissue. Some investigators strongly urge the routine use of these methods, although other investigators using these methods have had problems. These other investigators have shown that certain kinds of benign lesions (e.g., fibroadenoma, in younger patients) have high blood flow and are misinterpreted as malignant. These other methods are also difficult to use, because they require careful timing between the imaging and the injection. Finally, these methods cannot be used in screening, due to the risk to the patient, and the high cost of contrast material and administration. For these reasons, some investigators believe that these methods will have limited importance in breast cancer diagnosis. The new methods may provide more sensitive and specific assessment of malignancy, principally because the blood flow can be measured with much finer detail. The picture of this high blood flow can often tell which are the benign lesions and which are the cancerous ones. The new methods are perhaps the best hope of finding breast cancer as early as possible, in that they can provide, in a routine MR examination, high sensitivity to malignant breast lesions at the earliest stage, without the concerns associated with intravenous injections.