The aim of this study was to investigate a potential technique for image-guided minimally invasive neurosurgical interventions. Focused ultrasound (FUS) delivers thermal energy without an invasive probe, penetrating the dura mater, entering through the cerebrospinal fluid (CSF) space, or harming intervening brain tissue. We applied continuous on-line monitoring by MRI to demonstrate the effect of the thermal intervention on the brain tissue. For this, seven rabbits had a part of their skull removed to create access for the FUS beam into the brain through an acoustic window of 11 mm in diameter. Dura was left intact and skin was sutured. One week later, the rabbits were sonicated for 3 seconds with 21 W acoustic power, and the FUS focus was visualized with a temperature-sensitive T1-weighted MRI pulse sequence. The tissue reaction was documented over 7 days with T2-weighted images of the brain. The initial area of the central low signal intensity in the axial plane was .4 ± .3 mm2, and for the bright hyperintensity surrounding the lesion, it was 2.3 ± .6 mm2 (n = 7). In the coronal plane, the corresponding values were .4 ± .1 mm2 and 3.4 ± .9 mm2 (n = 5). The developing brain edema culminated 48 hours later and thereafter diminished during the next 5 days. Histology revealed a central necrosis in the white matter surrounded by edematous tissue with inflammatory cells. In summary, the image-guided thermal ablation technique described here produced a relatively small lesion in the white matter at the targeted location. This was accomplished without opening the dura or the need for a stereotactical device. MRI allowed on-line monitoring of the lesion setting and the deposition of thermal energy and demonstrated the tissue damage after the thermal injury. 相似文献
NMR techniques for temperature and pH measurements have attracted increasing interest in recent years, motivated in part by the growing importance of medical hyperthermia for the treatment of cancer. The chemical shifts of thulium 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetrakis(methylene phosphonate) (TmDOTP5-) have been studied as a function of temperature and pH. The results demonstrate that TmDOTP5- resonance shifts are highly sensitive to temperature (approximately 1.0 ppm/degrees C) and pH (approximately 3.2 ppm/pH unit) at clinically relevant field strengths. A new method is presented which utilizes two magnetically non-equivalent protons in TmDOTP5- for simultaneous NMR measurements of both temperature and pH. The difference in the chemical shift values of pairs of 1H resonances provides a temperature sensitivity of about 1.6 ppm/ degrees C. The technique is demonstrated in live rats undergoing ultrasound-induced hyperthermia therapy. 相似文献
This study investigated the design concepts and development of a multielement intracavitary ultrasound applicator for use in hyperthermia. A necessary condition imposed on these applicators is that each transducer element be separately powered and produce collimated beams. This way, the power deposition within the target volume can be controlled by varying the power to each element. Theoretical computer simulations (acoustic and thermal) and bench experiments were used to determine the constraints on the transducer element size and the spacing between them. These have shown that the length of the cylindrical segments (or subsections of) must be greater than approximately 10 lambda for proper collimation and that the spacing between them must be less than approximately 1.5 mm for uniform heating. With these design principles in mind, applicators were constructed using sections of cylindrical transducers (wall-thickness resonance). These were surrounded by temperature-controlled circulating water which was enclosed by a latex membrane. This allowed for acoustic coupling and additional control over the depth of the maximum temperature from the cavity wall. This depth could be varied between the cavity surface and up to 1.5 cm for circulating water temperatures between 5 and 42 degrees C, respectively. These applicators were tested in vivo and were able to induce controlled transrectal heating, at depths of 2-3 cm, in the canine rectum and prostate gland. 相似文献
Introduction: Treatment of several diseases of the brain are complicated by the presence of the skull and the blood-brain barrier (BBB). Focused ultrasound (FUS) and microbubble (MB)-mediated BBB treatment is a minimally invasive method to transiently increase the permeability of blood vessels in targeted brain areas. It can be used as a general delivery system to increase the concentration of therapeutic agents in the brain parenchyma.
Areas covered: Over the past two decades, the safety of using FUS+MBs to deliver agents across the BBB has been interrogated through various methods of imaging, histology, biochemical assays, and behavior analyses. Here we provide an overview of the factors that affect the safety profile of these treatments, describe methods by which FUS+MB treatments are controlled, and discuss data that have informed the assessment of treatment risks.
Expert opinion: There remains a need to assess the risks associated with clinically relevant treatment strategies, specifically repeated FUS+MB treatments, with and without therapeutic agent delivery. Additionally, efforts to develop metrics by which FUS+MB treatments can be easily compared across studies would facilitate a more rapid consensus on the risks associated with this intervention. 相似文献
STUDY OBJECTIVE: To evaluate renal and vasodilator effects of synthetic atrial natriuretic factor (ANF) in patients undergoing cardiopulmonary bypass (CPB) with special reference to the applicability of ANF as a diuretic and natriuretic. DESIGN: The study consisted of two parts. The first 15 consecutive patients in a university hospital received a pharmacologically effective bolus dose of 100 micrograms ANF, as demonstrated previously in other studies, or placebo. After analysis of the bolus data (see "Results" section below), the 12 subsequent patients were administered ANF 50 micrograms as a constant 30-min infusion at a rate of 1.67 micrograms/min or placebo. PATIENTS: The patients were scheduled for elective coronary artery bypass grafting operation. There was no evidence of congestive heart failure in any patient, and no one had an endocrine or renal disorder. INTERVENTIONS: After achievement of hypothermia (29 to 30 degrees C of rectal temperature) during CPB, a bolus dose of ANF 100 micrograms was given or an infusion of ANF 1.67 micrograms/min for 30 min, ie, a total dose of 50 micrograms was started. The control patients received placebo correspondingly. Intravenous fluids were administered according to a predetermined scheme. MEASUREMENTS AND MAIN RESULTS: For the pharmacologic effects of ANF urine volume, urinary sodium excretion and mean arterial pressure (MAP) were measured. Only three of the eight patients receiving the bolus dose of ANF had a diuretic and natriuretic response to the drug, and the responses were significantly related (r = 0.91, p less than 0.05 and r = 0.98, p less than 0.001, respectively) to the prevailing MAP at the time of the bolus administration. The bolus dose of ANF decreased MAP significantly (p less than 0.001 vs placebo) from 65 +/- 6 (mean +/- SEM) to 55 +/- 6 mm Hg within 5 min. The infusion of ANF did not affect MAP, but it increased urine output (16.1 +/- 5.0 ml/min, when the data obtained during the 30-min infusion and a 30-min period after the infusion were combined) and urinary sodium excretion (1,651 +/- 514 microEq/min) significantly (p less than 0.05 and p less than 0.01, respectively) as compared with the corresponding values of 3.3 +/- 1.1 ml/min and 386 +/- 141 microEq/min after placebo. CONCLUSIONS: Prevailing arterial pressure is an important determinant of the diuretic and natriuretic activity of synthetic ANF in patients undergoing CPB. A low-dose infusion of ANF (50 micrograms within 30 min) provides diuresis and natriuresis without significant changes in MAP in these patients. 相似文献
The ability to focus acoustic energy through the intact skull on to targets millimeters in size represents an important milestone in the development of neurotherapeutics. Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel, noninvasive method, which—under real-time imaging and thermographic guidance—can be used to generate focal intracranial thermal ablative lesions and disrupt the blood–brain barrier. An established treatment for bone metastases, uterine fibroids, and breast lesions, MRgFUS has now been proposed as an alternative to open neurosurgical procedures for a wide variety of indications. Studies investigating intracranial MRgFUS range from small animal preclinical experiments to large, late-phase randomized trials that span the clinical spectrum from movement disorders, to vascular, oncologic, and psychiatric applications. We review the principles of MRgFUS and its use for brain-based disorders, and outline future directions for this promising technology. 相似文献
The parameters of a spoiled gradient-echo (SPGR) pulse sequence have been optimized for in vivo localization of a focused ultrasound beam. Temperature elevation was measured by using the proton resonance frequency shift technique, and the phase difference signal-to-noise ratio (SNRδ ϕ) was estimated in skeletal muscle and kidney cortex in 10 rabbits. Optimized parameters included the echo time equivalent to T*2of the tissue, the longest repetition time possible with a 20-s sonication, and the flip angle equivalent to the Ernst angle. Optimal SPGR phase imaging can detect a sonication beam with a peak phase difference of 0.55 radian, which corresponds to a temperature elevation of 7.3°C. The sonication beam can be localized within one voxel (0.6 × 0.6 × 5 mm3) at power levels that are below the threshold for thermal damage of the tissue. 相似文献