Oana Craciunescu, Ellen Jones, Kimberly Blackwell, Terence Wong, Eric Rosen, Zeljko Vujaskovic, James MacFall, Vlayka Liotcheva, Michael Lora-Michiels, Leonard Prosnitz, Thaddeus Samulski, Mark Dewhirst
At Duke University Medical Center, selective LABC patients were treated on a protocol using neoadjuvant Myocet/Paclitaxel (ChT) and HT. With the purpose of generating perfusion/permeability parametric maps and to use gadolinium (Gd) enhancement curves to score and predict response to neoadjuvant treatment, a study was designed to acquire 3 sets of DE-MRI images along the 4 cycles of combined ChT and HT. A T1-weighted three-dimensional fast gradient echo technique was used over 30 minutes following bolus injection of Gd-based contrast agent. Perfusion/permeability maps were generated by fitting the signal intensity to a double exponential curve that generates washin (WiP) and washout (WoP), parameters that are associated with the tumors vascularity/permeability and cellularity. Based on the values of the WiP, the tumors were divided in lowWI (WiP < 100), mediumWI (100 200). During the HT treatments temperatures in the breast were measured invasively via a catheter inserted under CT guidance. Although minimum sampled temperatures give a crude indication of the temperature distribution, several thermal dose metrics were calculated for each of the HT fractions (e.g. T90, T50, T10). As expected, tumors that were more vascularized (i.e. higher WiP) heated less than tumors with low WiP, a degree on average. The adjuvant treatment also changed the shape and inhomogeneity of the perfusion/permeability maps, with dramatic changes after the first fraction in responders. The correlation between the thermal metrics and pathological response will be discussed, as well as possible correlation with other tumor physiology parameters. In conclusion, the Gd-enhancement analysis of DE-MRI images is able to generate information related to the tumor vascularity, permeability and cellularity that can correlate with the tumor's response to the neoadjuvant treatment in general, and to HT in particular. Work supported by a grant from the NCI CA42745.
P. J. Hoopes, K. Wishnow, Luanna Bartholomew, E. Jonsson, J. Williams, Karen Moodie, Terence Wong, R. Harris, Thomas Ryan, B. Stuart Trembly, Thomas McNicholas, J. Heaney
Five non-pharmacological, experimental, prostate (benign hyperplasia/cancer) treatment modalities including transurethral radiofrequency thermotherapy (TURT); transurethral microwave thermotherapy (TUMT); transurethral and transrectal microwave thermotherapy (TUMT/TRMT); interstitial laser coagulation (ILC); and interstitial cryotherapy (IC), are evaluated. These and other similar techniques are currently in various stages of development and clinical use. Most of these modalities produce relatively similar effects in tissue; however, each has pathophysiologic features and potential complications which may preference its use in a specific anatomical and/or disease situation. All treatments were performed using the canine prostate model, by the same investigators. Our studies have shown that although the canine prostate does not respond to injury exactly as the human prostate does, the effects are similar enough to be conceptually, and often specifically, valuable from efficacy and safety standpoints. Two of the five treatments evaluated (TURT, TUMT/TRMT) resulted in marked dilation of the prostatic urethra without significant parenchymal effect. Three of the treatments (IC, ILC, TUMT) resulted in parenchymal ablation with only minor dilation of the urethra. Although each technique has encouraging experimental findings, ultimate success will be determined by further definition of the instrumentation technique and appropriate clinical implementation.
From a reading of recent neurosurgical literature with a search focus on intracranial applications, a list of thermal agents and related minimally invasive techniques was drawn; this list was supplemented by our own research experience. Thermal agents which are either implemented in clinical practice or undergoing active research include: radioffequency current, laser light, microwave electromagnetic radiation, ultrasound and cryogens. Therapies include percutaneous coagulation of small targets which are less than half of one cubic centimeter as for rhizotomy for trigeminal neuralgia and pallidotomy for kinetic disorders, as well as interstitial hyperthermia and/or coagulation of large tumors which range up to centimeters in diameter. Implementation of a thermal agent for therapy evolves in a dynamic interaction between the specific technology and an understanding cf the tissue properties governing the agent’s therapeutic effect. Minimally invasive techniques require methods to define, visualize and approach targeted tissue, and to monitor (and thereby control) the extent of the thermal ‘lesion.’ Over the twentieth century, concomitant with advances in neurosurgery and radiology, technologies have been developed with which to approach the twenty-first century in pursuit of these minimally invasive thermal interventions which are, as of yet, new and underdeveloped.
The use of intraoperative MR image guidance has the potential to improve the precision, extent and safety of transsphenoidal pituitary resections. At Brigham and Women's Hospital, an open-bore configuration 0.5T MR system (SIGNA SP, GE Medical Systems, Milwaukee, WI) has been used to provide image guidance for nine transsphenoidal pituitary adenoma resections. The intraoperative MR system allowed the radiologist to direct the surgeon toward the sella turcica successfully while avoiding the cavernous sinus, optic chiasm and other sensitive structures. Imaging performed during the surgery monitored the extent of resection and allowed for removal of tumor beyond the surgeon's view in five cases. Dynamic MR imaging was used to distinguish residual tumor from normal gland and postoperative changes permitting more precise tumor localization. A heme-sensitive long TE gradient echo sequence was used to evaluate for the presence of hemorrhagic debris. All patients tolerated the procedure well without significant complications.
Advantages of MR imaging for guidance of minimally invasive procedures include exceptional soft tissue contrast, intrinsic multiplanar imaging capability, and absence of exposure to ionizing radiation. Specialized imaging sequences are available and under development which can further enhance diagnosis and therapy. Flow-sensitive imaging techniques can be used to identify vascular structures. Temperature-sensitive imaging is possible which can provide interactive feedback prior to, during, and following the delivery of thermal energy. Functional MR imaging and dynamic contrast-enhanced MRI sequences can provide additional information for guidance in neurosurgical applications. Functional MR allows mapping of eloquent areas in the brain, so that these areas may be avoided during therapy. Dynamic contrast enhancement techniques can be useful for distinguishing active tumor from tumor necrosis caused by previous radiation therapy. An open-configuration 0.5T MRI system (GE Signa SP) developed at Brigham and Women's Hospital in collaboration with General Electric Medical Systems is described. Interactive navigation systems have been integrated into the MRI system. The imaging system is sited in an operating room environment, and used for image guided neurosurgical procedures (biopsies and tumor excision), as well as minimally invasive thermal therapies. Examples of MR imaging guidance, navigational techniques, and clinical applications are presented.
Joachim Kettenbach, Nobuhiko Hata, Kagayaki Kuroda, Stuart Silverman, Terence Wong, Gary Zientara, Paul Morrison, Daniel Kacher, Dave Gering, Ron Kikinis, Ferenc Jolesz
Our goal was to investigate whether an open 0.5T MR-system with integrated frameless stereotactic guidance tools can provide sufficient intraoperative monitoring of interstitial laser therapy (ILT). Temperature-sensitive T1-weighted Fast- Spin-Echo (FSE)- or Spoiled Gradient-Echo sequences (SPGR) were applied and various image processing techniques (pixel- subtraction, phase mapping, optical flow computation) developed in order to control the thermal energy deposition during ILT in patients with brain- and liver tumors. While images from T1-weighted FSE- or SPGR sequences were acquired within 5 - 13 seconds, ILT lasted 2 to 26 minutes. Pixel subtraction or optical flow computation of T1-weighted images was performed within less than 110 msec. Alternating, phase- mapping of real- and imaginary components of SPGR sequences was performed within 220 msec. Pixel subtraction of T1- weighted images identified thermal changes in liver and brain tumors but could not evaluate the temperature values as chemical-shift based imaging, which was however, more affected by susceptibility effects and motion. Optical flow computation displayed the predicted course of thermal changes and revealed that the rate of heat deposition can be anisotropic, which may be related to heterogeneous tumor structure and/or vascularization.
Image guidance is one of the major challenges common to all minimally invasive procedures including biopsy, thermal ablation, endoscopy, and laparoscopy. This is essential for (1) identifying the target lesion, (2) planning the minimally invasive approach, and (3) monitoring the therapy as it progresses. MRI is an ideal imaging modality for this purpose, providing high soft tissue contrast and multiplanar imaging, capability with no ionizing radiation. An interventional/surgical MRI suite has been developed at Brigham and Women's Hospital which provides multiplanar imaging guidance during surgery, biopsy, and thermal ablation procedures. The 0.5T MRI system (General Electric Signa SP) features open vertical access, allowing intraoperative imaging to be performed. An integrated navigational system permits near real-time control of imaging planes, and provides interactive guidance for positioning various diagnostic and therapeutic probes. MR imaging can also be used to monitor cryotherapy as well as high temperature thermal ablation procedures sing RF, laser, microwave, or focused ultrasound. Design features of the interventional MRI system will be discussed, and techniques will be described for interactive image acquisition and tracking of interventional instruments. Applications for interactive and near-real-time imaging will be presented as well as examples of specific procedures performed using MRI guidance.
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