Alan R. Bleier

Magnetic resonance imaging of the acute effects of interstitial neodymium:YAG laser irradiation on tissues.

RATIONALE AND OBJECTIVES.Laser irradiation therapy in deep tissues requires a monitoring method other than visual guidance. Magnetic resonance imaging (MRI) can be used for this purpose because it visualizes soft tissue structures and heat distribution. METHODS.The authors performed interstitial laser irradiations in rat livers with various laser outputs and measured the sizes of laser-induced lesions. MRI of these lesions was done exvivo and compared with the histologic findings. Laser-induced lesions also were studied in rabbit brain, liver, and skeletal muscle to show the influences of tissue optical and thermal properties. Imaging of interstitial laser irradiation also was performed in vivo in rabbit brains. RESULTS.MRI depicted the laser-induced lesions produced with different laser outputs and tissue types. MRIs of rabbit brain in vivo effectively demonstrated the signal decrease during heating and acute tissue changes. CONCLUSION.MRI has potential for monitoring interstitial laser surgery or hyperthermia.

Two-site exchange revisited: a new method for extracting exchange parameters in biological systems.

A new analysis is presented which links real volume fractions, relaxation rates, and intracompartmental exchange rates directly with apparent volume fractions and relaxation rates obtained from biexponential fits of transverse magnetization decay curves. The analysis differs from previous methods in that measurements from two paramagnetic doping levels are used to close the two-site exchange equations. Both the new method and one previously described by Herbst and Goldstein (HG) have been applied to paramagnetically doped whole-blood data sets. Significant differences in the calculated exchange parameters are found between the two methods. A small dependence of the intracellular relaxation rate on extracellular paramagnetic agent concentration, assumed nonexistent with the HG method, is inferred from the new analysis. The analysis was also applied to published data on perfused rat hearts, and we obtained a limited assessment of two-site exchange in this system.

Response to and Control of Destructive Energy by Magnetic Resonance

Magnetic resonance imaging techniques can be used to control and monitor the deposition of destructive energy. The authors evaluated the feasibility of phosphorus-31 magnetic resonance spectroscopy for the control, monitoring, and prediction of the three-dimensional extent of tissue destruction during interstitial laser surgery. Characteristic metabolic changes were demonstrated within the lesion and in the adjacent normal tissue during the deposition of thermal energy.

Application of the maximum likelihood principle to separate exponential terms in T2 relaxation of nuclear magnetic resonance.

The method of maximum likelihood has been implemented for the estimation of multiple exponential components of T2 decay curves in spin echo NMR measurements on biologic tissues. Each Each component contributes an exponential term described by two parameters (initial amplitude and T2) to the T2 decay curve. The maximum likelihood method estimates the parameters and their standard errors for all terms simultaneously, avoiding the subjectivity inherent in methods such as graphical peeling. In the model used, it was assumed that water protons are compartmentalized and that the measured spin echo signals from the protons undergoing relaxation obey the Poisson distribution. A system of non-linear equations was derived and solved iteratively for the values of the exponential parameters which maximize the likelihood of obtaining the observed data under these assumptions. The approach was implemented for bi- and tri-exponential models on a MicroVAX II computer (Digital Equipment Corporation, Maynard, MA). Simulations of bi- and tri-exponential data, with and without system noise, were analyzed to assess the accuracy and reproducibility of the method. A subset of the simulations was repeated with non-linear least squares techniques and was compared to the results obtained with maximum likelihood. Rabbit muscle and gerbil brain samples were measured and analyzed with the maximum likelihood method. The simulations showed that within specific limits on relative sizes and relaxation rates of components, these parameters can be estimated with errors less than 5%. The comparison to non-linear least squares analysis showed that the maximum likelihood method is generally superior in estimating the parameters in difficult cases. The results from tissue measurements demonstrate that the method is effective even in cases where graphical peeling would clearly not yield reliable results.

Magnetic resonance imaging of interstitial laser photocoagulation

We have previously demonstrated the detection of reversible and irreversible changes on MR images oflaser energy deposition and tissue heating and cooling1. It is possible to monitor and control energy deposition during interstitial laser therapy. This presentation describes some first steps toward optimizing the power and total energy deposited in various tissues in vivo, by analyzing the irreversible tissue changes and their spatial distribution as revealed by spin echo imaging. We used various power settings of an Nd.YAG laser delivered by a fiber optic inserted into several tissues (brain, muscle, liver) of anesthetized rats and rabbits. MR imaging was performed at 1.9 T. Photothermally-produced lesions were seen on both T1- and Ta-weighted images. The overall size of the lesions correlated with the magnitude of the energy applied. The MR image appearance depended not only on the laser energy but also on the way it was delivered, on the type of tissue, and the MR pulse sequence applied. While Ti-weighted images adequately demonstrated an area of tissue destruction, T2- weighted images showed a more heterogeneous and more extensive lesion which could be better correlated with the complex histological representation of these lesions. Typically, when rabbit brain, liver, and muscle had been exposed to laser power of 2.5 Watts for a range of 55 to 120 seconds, depending on the tissue, a central area of signal void was surrounded by an inner hypointensity and an outer hyperintensity on T2-weighted images. The 3D extent of the lesions was well demonstrated on multislice images, providing correlation of the affected volumes seen on MRI with volumes seen in histological or histochemical preparations. We are developing an analytical model of laser heating and its effect on MR images to assess whether heating during imaging will produce unacceptable artifacts during surgery. The effect of heating is modeled as a change in magnetization during image acquisition. The region in which the change occurs is blurred by the Fourier transform of the change in magnetization as a function of time. Thus, blurring is minimized when changes occur slowly, compared to image acquisition times. We conclude that MRI can demonstrate the 3D extent of the lesions induced by lasers and can be used to investigate and optimize the control of induced tissue change within the affected volume.

Magnetic resonance imaging and spectroscopy to monitor and control experimental laser surgery

We have proposed the use of MRI for monitoring and control of interstitial laser surgery, in order to improve the accuracy and reduce the invasiveness of these procedures. To expand the knowledge base about the MR appearance of laser-induced tissue damage, we applied MR imaging and phosphorus-31 MR spectroscopy to detect the changes induced in various tissues by radiation from an Nd:YAG laser at 1060 nm wavelength delivered interstitially through a fiber optic waveguide. A range of laser energies was applied, and laser pulse parameters were varied. Proton MR images of the laser-produced lesions were compared with the histological appearance in brain and liver tissue of experimental animals. The spatial extent of laser effects differed among tissue types, and this was well reflected on MR images. The distribution of MR signal change resulting from different laser exposures was also demonstrated. Experimental laser surgery was performed in animal brain and bladder. Images taken before, during, and after laser irradiation allowed us to distinguish between reversible thermal and permanent effects. This information was utilized to tailor the destruction of preselected targets while minimizing damage to surrounding tissues. Qualitative changes were also revealed on phosphorus spectra. Irreversible lesions were characterized by overall line broadening and a decrease in AT?. There was also a large relative increase in the inorganic phosphate region of the spectrum. These demonstrations are a big step toward achieving our ultimate goal, the development of MR-controlled laser surgery.