Medical imaging is essential during the different steps of LITT procedures, from target definition to follow- up of induced lesions, through trajectory selection, fiber tracking, and prediction of final lesion size during the treatment. Monitoring of the thermal damage is essential to ensure that the all the lesion is treated, and
to prevent extension of damage to vital or functional structures. In the previous trials by Sugiyama et al.
(1990) and Roux et al. (1992a, b), laser probes were stereotactically inserted within tumors, and thermo- couple probes were stereotactically inserted a few millimeters away to control the temperature rise dur- ing procedures. This monitoring was obviously inva- sive and not precise, and there was a need for an in vivo method to test, monitor, and control the effects of medical lasers before, during, and after the LITT procedure.
Monitoring of LITT with ultrasound imaging has been studied in pigs by Schulze et al. (1998), and showed that temperature elevation could be moni- tored during the procedure. However, ultrasound-based monitoring techniques are not feasible for neuro- surgery, since the intact skull obstructs penetration of acoustic waves. Computed tomography (CT) is also not an appropriate imaging modality as it has low soft-tissue contrast resolution, and its sensitivity to early tissue changes following laser irradiation is poor as shown by Menovsky et al. (1996). On the con- trary, MRI has high soft tissue contrast, multiplanar imaging capabilities, high spatial resolution and tem- perature sensitivity, so that it is currently the best imaging modality to monitor LITT with good corre- lation with histology and to follow the evolution of treated lesions.
(a) MRI Thermal Imaging Sequences
Usefulness of MRI in LITT monitoring has been first described by Jolesz et al. (1988). In their in vitro and in vivo study, they showed the potential of MRI to map the spatial and temporal distribution of the effects of Nd:YAG lasers on cerebral tissue. During rabbit brain irradiation, they observed a complete loss of signal intensity at the fiber optic tip and a decrease in sig- nal intensity around it; the halo of decreased signal intensity surrounding the lesion at the fiber tip returned to normal intensity after irradiation. Therefore, they were able to use MR imaging to locate the target tis- sue to be treated and test the position of the laser, and they showed that MR images could demonstrate the spatial extent of both reversible and irreversible thermally induced tissue changes. The authors inter- preted the irreversible and complete signal loss as a combination of tissue water loss and altered tissue
t=0s t=18s t=54s t=103s t=139s t=187s
Fig. 20.1 Real time MRI thermal imaging (upper row) and necrosis prediction superimposed on anatomic images (from Carpentier et al.,2008)
water mobility, and the surrounding reversible signal loss as an effect of a local temperature rise. Tracz et al. (1992) also observed the appearance of a dark- to-hypointense region around the fiber tip during irra- diation of normal brains of anesthetized cats. However, these signal changes are not appropriate to monitor LITT. First, there is no possibility to distinguish sig- nal changes caused by coagulation and necrosis, and caused by temperature elevation. Moreover, as seen before, the induced necrosis evolves during the first 24–48 h after the treatment so that the acute image does not correspond to the final lesion.
To overcome these initial problems with MR lesion monitoring, temperature mapping was proposed to pre- dict real-time thermal damage and control the LITT procedure. In phantom materials and normal rabbit brain tissue in vivo, Bleier et al. (1991) investigated fast diffusion imaging with every 2 s acquisitions:
they were able to show the dynamics of temperature- related signal intensity changes in the regions irra- diated by an Nd-YAG laser. Meanwhile, the proton- resonance-frequency (PRF) method was used by De Porter (1995), which can provide reliable temperature quantification in vivo independently from the tissue type. Schulze et al. (1998) tested the PRF method in pig brains from cadavers. With temperature maps acquired every minute, they could visualize a nearly circular distribution of temperature around the fiber tip and expansion of the heated region during the course of LITT. Temperature at the vicinity of the probe reached more than 80◦C after 15 min, and they observed a steep temperature gradient with increas- ing distance to the laser fiber tip. Histological analysis showed that the border of the lesions corresponded
to 60–65◦C isotherms on the MRI maps. This led Kahn et al. (1998) to perform the first LITT proce- dure with MR PRF thermometry in a patient with an astrocytoma WHO II located adjacent to the left pre-central gyrus. During the irradiating procedure, they monitored the 60–65◦C isotherm to visually pre- dict the limits of the induced tissue damage (see Fig.
20.1). In addition, a good correlation was observed between this isotherm and an enhancing rim around the lesion on post-irradiation contrast-enhanced MRI.
No side effects were noted, the patient’s condition improved, and follow-up studies until 120 days after LITT showed a continuing regression of the lesion size. Kickhefel et al. (2010) showed that single shot echoplanar imaging (ss EPI) currently used sequences are faster and more precise for thermometry com- pared to gradient echo (GRE) or segmented echoplanar imaging (seg EPI) sequences.
(b) Real Time Computation
Recent progress in computer hardware has led to the development of software which can provide rapid pro- cessing of MR data to produce real-time quantitative temperature maps, estimates of thermal ablation zones, and computer-controlled feedback during treatments.
These methods are now currently used routinely in both preclinical and clinical studies. For example, in the clinical study by Carpentier et al. (2008), MR tem- perature mapping was obtained in a single image plane in the brain centered on the laser fiber every 6 s dur- ing ablation. Improved MR sequences can be further used to obtain 3D acquisitions through the treatment
volume, allowing for precise control of heat distribu- tion and necrosis prediction. Thus, adjacent normal tissue structures can be preserved and the safety of the procedure can be further improved. Furthermore, security processes built-in to the control software can allow for the determination of “security points” before the procedure (see Fig.20.2). Fiber damage or lesion of vital or functional structures can be avoided by positioning high-temperature limit points to limit tem- peratures below a pre-definite value. Other points can be used to confirm temperature elevation above a criti- cal value in order to obtain induced necrosis. Thanks to automatized control of laser delivery, laser irradiation can then be either stopped manually by the surgeon when the predicted thermal ablation zone is sufficient or automatically if any of the temperature limits is exceeded.
(c) Evolution of Brain Thermal Lesions on MRI
Many studies have described the appearance of thermally-induced lesions and their evolution on MRI.
Schawabe et al. (1997) and Kahn et al. (1994) described their findings in patients treated by LITT for primary or secondary brain tumors. Kangasniemi et al.
(2004) studied the evolution of LITT lesions after treat- ment of induced tumors in dog brains. In these studies, the results were similar and complementary.
The typical lesion architecture observed immedi- ately after LITT is comprised of five concentric zones:
the light guide, the central zone, the peripheral zone, a thin rim at the outer border of the peripheral zone, and perifocal edema. In T1-weighted images, the light
Fig. 20.2 Laser control delivery software with real time MRI thermometry analysis allows security processes: high- temperature limit security points to limit temperatures, Temperature follow-up points, desired target volume. The laser
irradiation can then be either stopped manually by the surgeon when the predicted thermal ablation zone is sufficient or auto- matically if any of the temperature limits is exceeded. (Courtesy of BioTex Visualase Inc.)
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Fig. 20.3 Contrast T1 MRI follow-up after a LITT treatment of a radiosurgery resistant metastasis
guide and peripheral zones are hypointense while the central zone is hyperintense. The perifocal edema is slightly hypointense. The thin rim at the border of the peripheral zone is hypointense with enhancement after gadolinium injection. Signal intensities of the differ- ent zones are opposite on T2-weighted images. The total size of lesions can increase by 0–45% in diam- eter during the first 10 days after LITT, essentially due to expansion of the peripheral zone. After the initial increase, the total lesion size decreases exponentially to reach 50% of the initial lesion size within a mean of 93 days (see Fig.20.3). Kangasniemi et al. (2004) observed an increase of lesion size up to 250% and explained this phenomenon by the different absorption characteristics of tissues at 980 nm. Perifocal edema is generally not apparent immediately following LITT treatments, but appears between 1 and 3 days after ther- apy with a maximum extent after 4–27 days (mean 6 days). The regression of edema can last 15–45 days.
The severity of edema generally does not coincide with the tumor grade or the applied laser energy. During the evolution of the lesion, the signal intensity of the central zone decreases progressively in T1-weighted images, while the signal intensity of the peripheral zone increases, resulting in more homogenous lesion, without differentiation into different zones. Moreover, the enhancing rim after gadolinium injection shows a continuous reduction in diameter and enhancement, and is visible even in late controls after treatment.
According to the authors, this zonal division in MRI corresponds to the zonal architecture described in histological studies. High signal intensity of the cen- tral zone in T1-weighted images may correspond to heat-induced methemoglobin conversion from deoxy- hemoglobin and high protein content fluid collections.
Low signal intensity in T1-weighted images and high
signal intensity in T2-weighted images of the periph- eral zone correspond to more or less important edema.