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Science to Practice |
Imaging Research Center Cincinnati Children's Hospital Medical Center,
3333 Burnet Ave, ML 5031
Cincinnati, OH 45229,
Diana.Lindquist@cchmc.org
SUMMARY
The promise of T1 relaxation in the rotating frame imaging is that it represents another magnetic resonance (MR) modality that can be used to detect nonspecific early treatment response and that can then be combined with other techniques, such as MR spectroscopic imaging or positron emission tomography (PET), to provide localized mechanistic information about treatment response.
THE SETTING
Patients with brain tumors face a particularly grim prognosis, with median survival times of 10–12 months (1,2). Median survival times have increased only slightly over the past few decades despite tremendous research efforts (1,3,4). The mainstays of treatment for primary brain tumors remain resection and radiation therapy, as well as adjuvant chemotherapy in some patients (3). Unfortunately, most imaging modalities are of limited use in determining treatment success, with success usually determined by a decrease in lesion size on follow-up studies. Gene therapy and other localized therapies offer new treatment options for these patients (4); however, with these cutting-edge therapies, early indicators of treatment success may be of even greater importance. In this issue of Radiology, Kettunen et al (5) describe an imaging technique that may be useful in determining early response to treatment.
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Kettunen et al (5) report the results of a study in which MR spin-lock contrast was used to follow tumor response to gene therapy. Spin-lock contrast is generated when the spins are locked for some time in the transverse plane after an initial excitation. The spins are then returned to the longitudinal plane, and conventional image acquisition is performed. This allows the measurement of an additional relaxation parameter, T1 in the rotating frame (T1
), which is a measure of the decay rate of the magnetization that is aligned with the B1 field of the applied radiofrequency locking pulse (6). T1 imaging may yield improved contrast sensitivity to tumors compared with conventional imaging methods. The sequence requires the application of a low-power, on-resonance radiofrequency pulse to magnetization in the transverse plane (7), which potentially limits the achievable strength of the locking pulse because of Food and Drug Administration limitations on radiofrequency absorption.
In their study, Kettunen and colleagues (5) measured T1 to monitor the treatment response of BT4C gliomas in rats at 4.7 T. Tumors were induced by implanting herpes simplex virus thymidine kinase–positive cells into the corpus callosum of female rats. Half of the rats received ganciclovir (a prodrug that is specific for herpes simplex virus thymidine kinase and is converted into toxic ganciclovir triphosphate [8]) for 8 days, while the others received saline. MR data were collected every 2 days. Conventional T1-weighted MR images were acquired, as well as data that were used to calculate T1, T2, T1, and apparent diffusion constant maps. Of these, the T1 and apparent diffusion constant maps showed early changes after the onset of treatment, with both maps being significantly (P < .05) different from baseline maps by day 4. T1 and T2 maps, however, showed significant (P < .05) changes at day 8 only. T1 was significantly (P < .05) correlated with the cell count in border regions of the tumor.
THE PRACTICE
Clinical use:
An imaging method that could be used to detect treatment response early in therapy would be extremely useful. Despite the high spatial resolution of conventional MR imaging methods, they are insensitive to subtle changes immediately after treatment and do not depict treatment response until relatively gross changes in size, contrast agent uptake, or diffusion occur. Other imaging modalities, such as PET, currently offer better prospects for the identification of molecular or metabolic changes associated with treatment response (9). The promise of T1 imaging is that it represents another MR modality that can be used to detect nonspecific early treatment response and that can then be combined with other techniques, such as MR spectroscopic imaging or PET, to provide localized mechanistic information about treatment response.
Future opportunities and challenges:
Gene therapy is one of the most promising avenues for treatment of glioblastomas. However, to fully realize the potential of gene therapy, methods must be developed to determine whether the therapeutic agent has reached its target, if and how much of the agent is being released, and whether the treatment is providing any benefit. Much remains to be done to achieve the goals of molecular imaging and answer these questions. Kettunen and colleagues (5) have made a valuable contribution to answering this last question, with a technique that is applicable to any therapy, not just gene therapy; however, further advances must be made before the first two questions can be answered. The answers to those questions will require the development of new contrast agents for MR imaging and PET, as well as the further development of imaging techniques to use them.
In this issue of Radiology, Kettunen et al (5) report that T1 maps are sensitive to changes in tumor growth as early as 4 days after the onset of gene therapy. Their results suggest that there is a role for MR imaging in monitoring the response to gene therapy.
ACKNOWLEDGMENTS
The author thanks Kim Cecil, PhD, for her helpful comments.
FOOTNOTES
See also the article by Kettunen et al in this issue.
References
) NMR relaxation with a microcomputer. Concepts Magn Reson 1998;10:157–166.[CrossRef]Related Article
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