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Biomedical subjects

F Jolesz

Publications and source records attributed to F Jolesz.

At least 19 recordsLinked to original sources

Focused ultrasound (HIFU) induces localized enhancement of reporter gene expression in rabbit carotid artery.

The development of accurate, safe, and efficient gene delivery remains a major challenge towards the realization of gene therapeutic prevention and treatment of cardiovascular diseases. In this study, we investigated the ability of high-intensity focused ultrasound (HIFU), a form of mechanical wave transmission, to act as a noninvasive tool for the enhancement of in vivo gene transfer into rabbit carotid arteries. Segments of the common carotid arteries of New Zealand white rabbits were isolated and infused with plasmid DNA encoding the reporter beta-galactosidase either with or without the addition of ultrasound contrast agent consisting of small (approximately 2-5 microm) gas-filled human albumin microspheres to augment cavitation. Infused arteries were exposed to pulsed ultrasound for 1 min (frequency 0.85 MHz, burst length 50 ms, repetition frequency 1 Hz, duration 60 s, peak pressure amplitude of 15 MPa). At 6.3 MPa, HIFU enhanced gene expression eight-fold, and 17.5-fold in the presence of contrast. We found increasing amounts of beta-galactosidase expression in the carotid vessel with increasing pressure amplitude. This dose-response relation was present with and without contrast. Without contrast, no vessel damage was detected up to 15 MPa, while the addition of contrast induced side effects above a threshold of 6.3 MPa peak pressure. The entire procedure was feasible and safe for the animals, and the results suggest that HIFU has the potential to assist in the noninvasive spatial regulation of gene transfer into the vascular system.

Animals↗

MRI measures of entorhinal cortex vs hippocampus in preclinical AD.

BACKGROUND: MRI measures of the entorhinal cortex and the hippocampus have been used to predict which nondemented individuals with memory problems will progress to meet criteria for AD on follow-up, but their relative accuracy remains controversial. OBJECTIVES: To compare MRI measures of the entorhinal cortex and the hippocampus for predicting who will develop AD. METHODS: MRI volumes of the entorhinal cortex and the hippocampus were obtained in 137 individuals comprising four groups: 1) individuals with normal cognition both at baseline and after 3 years of follow-up (n = 28), 2) subjects with memory difficulty but not dementia both at baseline and after 3 years of follow-up (n = 73), 3) subjects with memory difficulty at baseline who were diagnosed with probable AD within 3 years of follow-up (n = 21), and 4) patients with mild AD at baseline (n = 16). RESULTS: Measures of both the entorhinal cortex and the hippocampus were different for each of the pairwise comparisons between the groups (p < 0.001) and were correlated with tests of memory (p < 0.01). However, the volume of the entorhinal cortex differentiated the subjects from those destined to develop dementia with considerable accuracy (84%), whereas the measure of the hippocampus did not. CONCLUSION: These findings are consistent with neuropathologic data showing substantial involvement of the entorhinal cortex in the preclinical phase of AD and suggest that, as the disease spreads, atrophic change develops within the hippocampus, which is measurable on MRI.

Aged↗

MRI monitoring of the thermal ablation of tissue: effects of long exposure times.

MRI-derived thermometry based on the temperature-dependence of the proton resonant frequency (PRF) is extremely sensitive to changes in tissue unrelated to temperature changes, including tissue swelling. This study investigated the maximum amount of time that this phase-subtraction-based method can be used to accurately monitor temperature changes in vivo. Long-duration focused ultrasound sonications were delivered in rabbit thigh muscle with a phased-array transducer, and the time that tissue swelling began was monitored. Tissue swelling began to occur at about one minute. The temperature correlated well with an implanted thermocouple up to this time. After this time, severe artifacts in the phase-difference maps were observed. The thermal dose model predicted the extent of tissue damage well for subsequent one minute sonications. These results will have implications for MRI guidance of thermal therapies with long exposure times.

Animals↗

Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease.

We used magnetic resonance imaging (MRI) measurements to determine whether persons in the prodromal phase of Alzheimer's disease (AD) could be accurately identified before they developed clinically diagnosed dementia. Normal subjects (n = 24) and those with mild memory difficulty (n = 79) received an MRI scan at baseline and were then followed annually for 3 years to determine which individuals subsequently met clinical criteria for AD. Patients with mild AD at baseline were also evaluated (n = 16). Nineteen of the 79 subjects with mild memory difficulty "converted" to a diagnosis of probable AD after 3 years of follow-up. Baseline MRI measures of the entorhinal cortex, the banks of the superior temporal sulcus, and the anterior cingulate were most useful in discriminating the status of the subjects on follow-up examination. The accuracy of discrimination was related to the clinical similarity between groups. One hundred percent (100%) of normal subjects and patients with mild AD could be discriminated from one another based on these MRI measures. When the normals were compared with the individuals with memory impairments who ultimately developed AD (the converters), the accuracy of discrimination was 93%, based on the MRI measures at baseline (sensitivity = 0.95; specificity = 0.90). The discrimination of the normal subjects and the individuals with mild memory problems who did not progress to the point where they met clinical criteria for probable AD over the 3 years of follow-up (the "questionables") was 85% and the discrimination of the questionables and converters was 75%. The apolipoprotein E genotype did not improve the accuracy of discrimination. The specific regions selected for each of these discriminations provides information concerning the hierarchical fashion in which the pathology of AD may affect the brain during its prodromal phase.

Aged↗

Periventricular white matter injury in the premature infant is followed by reduced cerebral cortical gray matter volume at term.

Periventricular white matter injury, that is, periventricular leukomalacia (PVL), the dominant form of brain injury in the premature infant, is the major neuropathological substrate associated with the motor and cognitive deficits observed later in such infants. The nature of the relationship of this lesion to the subsequent cognitive deficits is unclear, but such deficits raise the possibility of cerebral cortical neuronal dysfunction. Although cortical neuronal necrosis is not a prominent feature of brain injury in premature infants, the possibility of a deleterious effect of PVL on subsequent cerebral cortical development has not been investigated. An advanced quantitative volumetric three-dimensional magnetic resonance imaging technique was used to measure brain tissue volumes at term in premature infants with earlier ultrasonographic and magnetic resonance imaging evidence of PVL (mean gestational age at birth, 28.7 +/- 2.0 weeks; n = 10), in premature infants with normal imaging studies (mean gestational age at birth, 29.0 +/- 2.1 weeks; n = 10), and in control term infants (n = 14). Premature infants with PVL had a marked reduction in cerebral cortical gray matter at term compared with either premature infants without PVL or normal term infants (mean +/- SD: PVL, 157.5 +/- 41.5 ml; no PVL, 211.7 +/- 25.4 ml; normal term, 218.8 +/- 21.3 ml). As expected, a reduction in the volume of total brain myelinated white matter was also noted (mean +/- SD: PVL, 14.5 +/- 4.6 ml; no PVL, 23.1 +/- 6.9 ml; normal term, 27.6 +/- 10.3 ml). An apparent compensatory increase in total cerebrospinal fluid volume also was found (mean +/- SD: PVL, 64.5 +/- 15.2 ml; no PVL, 52.0 +/- 24.1 ml; normal term, 32.9 +/- 13.5 ml). PVL in the premature infant is shown for the first time to be followed by impaired cerebral cortical development. These findings may provide insight into the anatomical correlate for the intellectual deficits associated with PVL in the premature infant.

Basal Ganglia↗

Assessing suspected spinal cord compression: a multidisciplinary outcomes analysis of 342 episodes.

The object of this work was to evaluate the assessment and document the outcomes of cancer patients with suspected spinal cord compression (SCC). In a retrospective cohort study of 342 episodes of suspected SCC in cancer patients evaluated by computed tomography (CT) of the spine, a multidisciplinary team of neurologists, radiologists, and oncologists assessed the impact of varying the anatomical criterion for SCC and including new SCC diagnosed shortly after definitive radiographical imaging. We developed a logistic regression model to identify independent clinical predictors of SCC, including the natural history of the underlying cancer as well as neurological and radiological risk factors. Management of suspected SCC infrequently involved neurology consultation (21% of episodes). The frequency of SCC increased more than four-fold when the definition was expanded to include epidural cancer rather than spinal cord displacement only (36% vs. 8%), and 90-day clinical follow-up identified few new lesions not evident on definitive imaging studies. Clinical information about the course of cancer (documentation and duration of metastatic cancer) added independent predictive information to that yielded by neurological assessment and prior imaging studies in a multiple regression model. The a priori predicted risk of SCC, which ranged from 4% to 87% in this study, may vary enough to affect treatment strategies, although our population may have excluded very-low-risk patients. Consistent anatomical definitions of SCC, clinical follow-up of definitive imaging studies and the addition of information on the natural history of cancer to traditional neurological and radiographical evaluation may all improve clinical assessment of suspected SCC in cancer patients.

Adolescent↗

Transsphenoidal resection of pituitary adenomas in an intraoperative MRI unit.

BACKGROUND: Transsphenoidal resection is a well known surgical procedure used in the treatment of sellar and parasellar lesions. In certain cases, operative identification of the lesion and achieving a complete resection can be problematic. We describe a surgical image guidance method using an intraoperative MRI which provides definitive identification of a lesion and verification of a complete resection. MATERIAL AND METHODS: Five patients with pituitary macroadenomas underwent transsphenoidal resection of their tumors in the intraoperative MRI unit at the Brigham and Women's Hospital. This unit was developed as a collaboration between General Electric and BWH and is an open configuration 0.5 Tesla MR imager in which surgery can be performed with real time, intraoperative MR guidance. RESULTS: The transsphenoidal resections were performed in a standard fashion in this unit. Intraoperative imaging allowed accurate localization of the lesions, identification of pertinent surrounding structures, and the evaluation of the extent of each resection. In two patients, the resection would have been considered complete based on the surgical field of view alone but MR imaging allowed remaining tissue to be identified. Developing clot was seen in one patient after a fat graft had been placed. CONCLUSION: The intraoperative MR is a surgical modality by which transsphenoidal resection of pituitary macroadenomas can be performed using real-time image guidance. It allows definitive identification of the tumor and an immediate evaluation of whether resection is complete. It also can monitor the occurrence of intraoperative complications such as hemorrhage. This revolutionary device can be an important tool for the surgical management of pituitary tumors.

Adenoma↗

Magnetic resonance imaging-guided focused ultrasound synovectomy.

OBJECTIVE: To investigate the feasibility of magnetic resonance imaging (MRI)-guided high power focused ultrasound (FUS) to perform synovectomy noninvasively. METHODS: Five New Zealand white male rabbit knees with experimentally induced arthritis underwent MRI-guided thermal surgery by high power (60 W/10 s) sonication. Evidence of tissue coagulation was monitored during the procedure and confirmed by gross and microscopic evaluation and MRI. RESULTS: Partial synovectomy was performed in five animals. Necrotized synovial tissue was observed on gross and microscopic evaluation. Visible signal intensity alterations including high signal intensity on T2-weighted (T2W) images and lack of contrast-enhancement on T1-weighted (T1W) post-contrast, post-sonication images were characteristic and reproducible. CONCLUSION: Our results demonstrate the ability of high power sonication to destroy synovial tissue in vivo.

Animals↗

Craniotomy for tumor treatment in an intraoperative magnetic resonance imaging unit.

OBJECTIVE: The complex three-dimensional anatomic features of the brain and its vulnerability to surgical intervention make the surgical treatment of intracranial tumors challenging. We evaluated the surgical treatment of supratentorial tumors using intraoperative magnetic resonance imaging (MRI), which provides real-time guidance, allows localization of intracranial tumors and their margins, and facilitates continuous assessment of surgical progress. METHODS: Sixty patients underwent craniotomies for tumor treatment in the General Electric intraoperative MRI unit at the Brigham and Women's Hospital (Boston, MA) during a 1-year period. The patients selected were those with intracranial tumors that were considered difficult to resect because of their locations or previous incomplete operations. Twenty-nine low-grade and 19 high-grade gliomas, 8 metastatic lesions, 2 meningiomas, 1 pineoblastoma, and 1 astroblastoma were resected. RESULTS: Tumors were accurately localized and targeted, and the extent of resection, as well as any intraoperative complications, could be immediately assessed during surgery. Marked brain shifting occurred during the procedures, and repeated intraoperative imaging allowed surgical accommodation for this shifting. In more than one-third of the cases, intraoperative imaging showed residual tumor when resection appeared complete on the basis of surgical observation alone. CONCLUSION: Intraoperative MRI is a revolutionary tool for the surgical treatment of brain tumors, providing observation of the procedure as it is being performed. With intraoperative MRI, tumor resection is safer, the extent of resection can be directly evaluated, and intraoperative complications can be noted if they occur. Outcomes after resection depend on minimizing injury to normal brain tissue and achieving maximal tumor resection. The use of intraoperative MRI directly affects these factors.

Adult↗

Three-dimensional image reconstruction for low-grade glioma surgery.

Three-dimensional image reconstruction for preoperative surgical planning and intraoperative navigation for the resection of low-grade gliomas was performed in 20 patients. Thirteen of these surgeries were performed while the patient received a local anesthetic to allow for cortical mapping. Ninety percent of the patients were functionally intact postoperatively. The authors propose that the combination of the three-dimensional image reconstruction and surgical navigation, in conjunction with intraoperative cortical mapping, provides an additional means for surgeons to improve the safety and precision of the procedures.

Journal Article↗

Surgical treatment of low-grade gliomas in the intraoperative magnetic resonance imager.

Radical resection of low-grade gliomas can decrease the incidence of recurrence, the time to tumor progression, and the incidence of malignant transformation. The authors present a series of 25 patients who underwent craniotomy and resection of low-grade tumor in an intraoperative magnetic resonance (MR) imager. This is an open configuration 0.5-tesla imager developed by The Brigham and Women's Hospital and General Electric, in which a patient can be placed to undergo surgery. Gross-total removal was accomplished under real-time image guidance. These intraoperative images allow definitive localization and targeting of the lesions and accommodate anatomical changes that may occur during surgery. The authors consistently found that the extent of abnormality seen on the intraoperatively obtained films of resection was larger than that apparent in the surgical field of view alone. Intraoperative imaging made accurate surgical identification of these abnormal areas and subsequent resection possible. Patients with tumors adjacent to or within motor or language cortex underwent resection while awake, with monitoring of neurological function. In these cases, an aggressive resection without increased neurological morbidity was accomplished using the image guidance in conjunction with serial testing. A 1-month postoperative MR image was obtained in all patients. These correlated with the final intraoperative images obtained after the resection was completed. Only one patient had a mild postoperative deficit that remained at the 1-month follow-up examination. As the long-term outcome in patients with low-grade gliomas has been shown to correspond to the degree of resection, surgical resection in which intraoperative MR imaging guidance is used can be an invaluable modality in the treatment of these tumors.

Journal Article↗

Virtual otoscopy.

Imaging techniques assist the surgeon in diagnosis of disease, surgical planning, and providing image guidance during surgery. Endoscopy has the drawback of being a minimally invasive procedure and limiting visualization to the inner surface of the lumen. Ultrasound, CT, and MR imaging show volumes of tissue beyond the lumen wall; however, their planar, two-dimensional representations require mental reconstruction of anatomic structures, which often proves difficult with the small, complex structures within the temporal bone. To improve three-dimensional visualization of the inner ear, we successfully completed a virtual model that can be displayed as a contiguous, three-dimensional luminal view, known as virtual otoscopy, which emulates traditional endoscopy. A concomitant global view and a view of the related CT slice adds a distinct advantage in the presentation and study of this complex organ. Advances in computer and software technology may overcome the time and cost factors that, at present, limit widespread use of virtual otoscopy. Overall, virtual otoscopy stands as a promising new visualization technique for elucidation of the middle ear, inner ear, and temporal bone structures.

Computer Simulation↗

Suspected spinal cord compression in breast cancer patients: a multidisciplinary risk assessment.

Breast cancer is the most common cause of metastatic epidural spinal cord compression (SCC) in women, and this condition results in significant neurologic dysfunction and morbidity. Prior studies of patients with suspected SCC did not employ multivariate analysis techniques, often included persons with a wide variety of malignancies, and generally focused on identifying associated neurologic and radiologic features. We therefore conducted a study examining a more comprehensive set of potential clinical risk factors in breast cancer patients with suspected SCC. We retrospectively analysed 123 episodes of suspected SCC among 93 breast cancer patients evaluated by spine computed tomography (CT) scanning. Multiple logistic regression analysis was employed to identify independent predictors of SCC. Clinically significant metastatic epidural cancer was defined as thecal sac compression (TSC), which occurred in 33 episodes (27%). Four independent predictors of TSC were identified and included oncologic features (known bone metastases > or = 2 years, metastatic disease at initial diagnosis) in addition to neurologic and radiologic features (objective weakness, vertebral compression fracture on spine radiograph). These four predictors stratified episodes into subgroups with widely varying risks of TSC, ranging from 12% (0 risk factors) to 85% (> or = 3 risk factors). These results suggest that the evaluation of breast cancer patients with suspected SCC should include clinical information about their disease course in addition to neurologic examination and prior imaging studies. If confirmed, these predictors may help clinicians assess risk in this patient population.

Adult↗

Excision of cortical dysplasia in the language area with use of a surgical navigator: a case report.

PURPOSE: We have developed an intraoperative optical tracking-based navigational system that allows localization in the operative space. Using three-dimensional reconstruction, this system has provided precise spatial information for intraoperative cortical mapping in patients with intractable epilepsy in whom the lesion lies close to eloquent cortex. METHODS: A 23-year-old man with intractable complex partial seizures (CPS) presented to our institution. Proton-density magnetic resonance imaging (MRI) showed a 3-cm lesion which lay 2 cm beneath the left frontal operculum. A three-dimensional model of the patient was reconstructed using MR modalities. Intraoperatively, subdural grid and strips were placed over the lesion and their electrodes were registered to the three-dimensional model, which was displayed on a monitor. The navigational system was used to localize each electrode on the three-dimensional model. By the second operation, the sites of seizure activity were established and recorded on the three-dimensional model. A bipolar stimulator was also used to determine the speech area. RESULTS: The lesion, which proved to be cortical dysplasia, was removed completely and the cortical speech area was avoided. During the postoperative period, the patient had no neurological symptoms and no seizure activity. CONCLUSIONS: The localization of a lesion and its correlation with epileptogenic foci is important in optimizing treatment in patients with cortical dysplasia. Our navigational system provided accurate localization of the lesion and correlation with the epileptogenic focus and related eloquent cortex. We believe that the safe removal of the lesion was facilitated by this system.

Adult↗

Diffusion-weighted MR imaging in hypertensive encephalopathy: clues to pathogenesis.

PURPOSE: Hypertensive encephalopathy, a complex of cerebral disorders, including headache, seizures, visual disturbances, and other neurologic manifestations, is associated with a variety of conditions in which blood pressure rises acutely. It has been ascribed to either exuberant vasospasm with ischemia/infarction or breakthrough of autoregulation with interstitial edema. Diffusion-weighted MR imaging may be used to determine whether the edema in hypertensive encephalopathy is cytotoxic or vasogenic in origin. METHODS: Diffusion-weighted imaging was performed using the double line scan diffusion imaging technique on a 1.5-T MR system. Seven patients with hypertensive encephalopathy were imaged within 1 day of the onset of their symptoms. Apparent diffusion coefficient maps as well as low and high b-factor images were acquired. The two-tailed paired Student's t-test was used to compare the apparent diffusion coefficients in edematous brain regions with those of normal white matter. RESULTS: In all cases the apparent diffusion coefficient maps of the patients with hypertensive encephalopathy showed increased signal in regions corresponding to increased T2 signal on standard T2-weighted (low b-factor) images. Quantitative apparent diffusion coefficients in regions of abnormal T2 signal were 1.36 +/- 0.14 microm2/ms, compared with 0.80 +/- 0.05 microm2/ms in normal white matter. Diffusion-weighted (high b-factor) T2-weighted images did not show abnormal signal. CONCLUSION: Diffusion-weighted MR imaging shows that the edema in hypertensive encephalopathy is of vasogenic origin and does not represent ischemia or infarction. This finding may have therapeutic implications.

Adult↗

Semi-automated extraction of brain contours from MRI.

We compared brain volumes computed by trained operators using the BRAIN-MAP algorithm, which automatically extracts the contours of the brain from gradient-echo magnetic resonance images. The images of 19 subjects randomly selected from a group of normals and a group of patients with dementia were included. BRAIN-MAP found brain perimeters that were on the average ca. 3% tighter than those obtained by two experienced operators. Between-operator and within-operator reproducibility of the analyses were also estimated and found to be (-0.13 +/- 0.51)% and (-0.63 +/- 0.08)%, respectively. Replicate volume measurement by the computer alone provided a reproducibility of (0.44 +/- 0.46)%.

Adult↗

Three-dimensional reconstruction and surgical navigation in pediatric epilepsy surgery.

We have used MRI-based three-dimensional (3D) reconstruction and a real-time, frameless, stereotactic navigation device to facilitate the removal of seizure foci in children suffering from intractable epilepsy. Using this system, the location of subdural grid and strip electrodes is recorded on the 3D model to facilitate focus localization and resection. Ten operations were performed, including 2 girls and 8 boys ranging in age from 3 to 17, during which 3D reconstruction and surgical instrument tracking navigation was used. In all the cases, the patients tolerated the procedure well and showed no postoperative neurological deficits. We believe this to be a valuable tool for a complete and safe resection of seizure foci, thereby reducing the incidence of postoperative neurological deficits and significantly improving the overall quality of life of the patients.

Adolescent↗

Noninvasive arterial occlusion using MRI-guided focused ultrasound.

The purpose of this work was to test the hypothesis that reproducible and sustainable arterial occlusion can be induced by focused ultrasound energy deposition noninvasively within deep tissue. An MRI-compatible focused ultrasound transducer was used to sonicate a branch of the renal artery (diameter about 0.6 mm) in vivo (nine rabbits). An intravenous MRI contrast agent bolus was injected about 30 min and up to 7 days after the sonication. After follow-up, in vitro magnification x-ray angiograms were obtained and the kidneys were fixed in formaldehyde for histologic study. The ultrasound pulses resulted in complete cessation of blood flow, as shown by the gradient echo images. In seven of the nine rabbits, a wedge-shaped unenhanced area was seen at the part of the kidney that was perfused by the vessel after the contrast agent injection. This area extended laterally (outside of the sonicated volume) to the cortical surface of the kidney. The x-ray angiograms showed that the artery was completely occluded. Postmortem histologic evaluation showed an infarcted tissue volume corresponding to the wedge shape seen in the images. This study showed that appropriately focused ultrasound can be used to close arteries noninvasively. This finding has significant clinical potential.

Angiography↗