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Ferenc Jolesz

Publications and source records attributed to Ferenc Jolesz.

8 recordsLinked to original sources

Geometrically constrained two-tensor model for crossing tracts in DWI.

MR diffusion tensor imaging (DTI) of the brain and spine provides a unique tool for both visualizing directionality and assessing intactness of white matter fiber tracts in vivo. At the spatial resolution of clinical MRI, much of primate white matter is composed of interdigitating fibers. Analyses based on an assumed single diffusion tensor per voxel yield important information about the average diffusion in the voxel but fail to reveal structure in the presence of crossing tracts. Until today, all clinical scans assume only one tensor, causing potential serious errors in tractography. Since high angular resolution imaging remains, so far, untenable for routine clinical use, a method is proposed whereby the single-tensor field is augmented with additional information gleaned from standard clinical DTI. The method effectively resolves two distinct tract directions within voxels, in which only two tracts are assumed to exist. The underlying constrained two-tensor model is fitted in two stages, utilizing the information present in the single-tensor fit. As a result, the necessary MRI time can be drastically reduced when compared with other approaches, enabling widespread clinical use. Upon evaluation in simulations and application to in vivo human brain DTI data, the method appears to be robust and practical and, if correctly applied, could elucidate tract directions at critical points of uncertainty.

Animals↗

Brain arterioles show more active vesicular transport of blood-borne tracer molecules than capillaries and venules after focused ultrasound-evoked opening of the blood-brain barrier.

Previously, activation of vesicular transport in the brain microvasculature was shown to be one of the mechanisms of focused ultrasound-induced blood-brain barrier (BBB) opening. In the present study, we aimed to estimate the rate of the transendothelial vesicular traffic after focused ultrasound sonication in the rabbit brain, using ultrastructural morphometry and horseradish peroxidase (HRP) as a tracer. In the capillaries, the mean endothelial pinocytotic densities (the number of HRP-containing vesicles per microm(2) of the cell cytoplasm) were 0.9 and 1.05 vesicles/microm(2) 1 h after sonication with ultrasound frequencies of 0.69 and 0.26 MHz, respectively. In the arterioles, these densities were 1.63 and 2.43 vesicles/microm(2), values 1.8 and 2.3 times higher. In control locations, the densities were 0.7 and 0.14 vesicles/microm(2) for capillaries and arterioles, respectively. A small number of HRP-positive vesicles were observed in the venules. Focal delivery of HRP tracer was also observed in light microscopy. The results indicate that the precapillary microvessels play an important role in macromolecular transcytoplasmic traffic through the ultrasound-induced BBB modulation, which should be considered in the future development of trans-BBB drug delivery strategies.

Animals↗

Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles.

Local blood-brain barrier (BBB) opening is an advantageous approach for targeted drug delivery to the brain. Recently, it has been shown that focused ultrasound (US) exposures (sonications), when applied in the presence of preformed gas bubbles, caused magnetic-resonance (MR) proven reversible opening of the BBB in targeted locations. The cellular mechanisms of such transient barrier disruption are largely unknown. We investigated US-induced changes in endothelial cell fine morphology that resulted in the BBB opening in rabbits. To obtain evidence for the passage of blood-borne macromolecules through the opened transvascular routes, an immunocytochemical procedure for endogenous immunoglobulinG (IgG) was performed, in addition to the routine electron microscopy. An increased number of vesicles and vacuoles, fenestration and channel formation, as well as opening of some tight junctions, were seen in capillaries after low-power (0.55 W) sonication. Immunosignals presented in some of the vesicles and vacuoles, in the cytoplasmic channels and, so rarely, in intercellular clefts; immunosignals could also be seen in neuropil around the blood vessels. Damage to the cellular ultrastructure was not seen in these areas. However, cell destruction and leakage of IgG through defects of the endothelial lining took place at 3 W sonications. The data reveals that several mechanisms of transcapillary passage are possible after such sonications: 1. transcytosis; 2. endothelial cell cytoplasmic openings--fenestration and channel formation; 3. opening of a part of tight junctions; and 4. free passage through the injured endothelium (with the higher power sonications). These findings could be considered in further development of the strategy for drug delivery to brain parenchyma.

Animals↗

Structural modeling of dynamic changes in memory and brain structure using longitudinal data from the normative aging study.

This is an application of new longitudinal structural equation modeling techniques to time-dependent associations of memory and brain structure measurements. There were 225 participants aged 30-80 years at baseline who were measured again after a 7-year interval on both the lateral ventricular size and Wechsler memory score. Multiple regression analyses show nonlinear associations with age but no relationships among longitudinal changes. Mixed-effects latent growth curve analyses and analyses based on latent difference scores indicate that longitudinal changes in both variables are reasonably well described by an exponential or dual change model. Bivariate dynamic structural equation modeling analyses indicate age-lagged changes operate in a coupled-over-time fashion, with the brain measure (lateral ventricular size) as a leading indicator in time of memory (Wechsler memory score) declines.

Adult↗

MRI guidance of focused ultrasound therapy of uterine fibroids: early results.

OBJECTIVE: The purpose of this study was to explore our hypothesis that MRI-guided focused ultrasound therapy for the treatment of uterine fibroids will lead to a significant reduction in symptoms and improvement in quality of life. We describe focused ultrasound therapy applications and the method for monitoring the thermal energy deposited in the fibroids, including the MRI parameters required, in a prospective review of 108 treatments. MATERIALS AND METHODS: Patients presenting with symptomatic uterine fibroids who attained a minimal symptom severity score and who would otherwise have been offered a hysterectomy were recruited. Thermal lesions were created within target fibroids using an MRI-guided focused ultrasound therapy system. The developing lesion was monitored using real-time MR thermometry, which was used to assess treatment outcome in real time to change treatment parameters and achieve the desired outcome. Fibroid volume, fibroid symptoms, and quality-of-life scores were measured before treatment and 6 months after treatment. Adverse events were actively monitored and recorded. RESULTS: In this study, 79.3% of women who had been treated reported a significant improvement in their uterine fibroid symptoms on follow-up health-related quality-of-life questionnaires, which supports our hypothesis. The mean reduction in fibroid volume at 6 months was 13.5%, but nonenhancing volume (mean, 51 cm(3)) remained within the treated fibroid at 6 months. CONCLUSION: This early description of MRI-guided focused ultrasound therapy treatment of fibroids includes follow-up data and shows that, although the volume reduction is moderate, it correlates with treatment volume and the symptomatic response to this treatment is encouraging.

Adult↗

Late genitourinary and gastrointestinal toxicity after magnetic resonance image-guided prostate brachytherapy with or without neoadjuvant external beam radiation therapy.

BACKGROUND: This study was designed to estimate the rates of late genitourinary (GU) and rectal toxicity after magnetic resonance image (MRI)-guided prostate brachytherapy exclusively or in conjunction with external beam radiation therapy (EBRT). METHODS: Between November 1997 and April 2002, 201 patients with category T1C prostate carcinoma (according to the 2002 American Joint Committee on Cancer staging criteria), prostate specific antigen levels < 10 ng/mL, and biopsy Gleason score 3 + 4 disease were treated with MRI-guided brachytherapy exclusively or in conjunction with EBRT. The MRI-guided technique was designed to spare the urethra based on delivery of the prescription dose to the peripheral zone exclusively. The Kaplan-Meier method was used to estimate rates of freedom from late GU and rectal toxicity. Comparisons were made using a log-rank test. RESULTS: At a median follow-up of 2.8 years (range, 0.5-5.0 years), the 4-year estimates of rectal bleeding requiring coagulation for patients who underwent implantation therapy, compared with patients who received combined-modality therapy, were 8% versus 30%, respectively (log-rank P value = 0.0001). Although erectile dysfunction was common (range, 82-93%), with the use of sildenafil citrate (Viagra), it was estimated that at least two-thirds of patients had erectile function comparable to or superior to baseline function, independent of whether they received monotherapy or combined-modality therapy (P = 0.46). The 4-year estimate of freedom from radiation cystitis was 100% versus 95% (P = 0.01) for patients who received monotherapy and patients who received combined-modality therapy, respectively. No urethral strictures were observed, and no patients underwent postimplantation transurethral resection of the prostate. CONCLUSIONS: In the current study, rectal bleeding after MRI-guided prostate brachymonotherapy was infrequent, and urethral and bladder toxicity is reported to be rare and may be attributed to the urethral-sparing technique of the MRI-guided approach.

Aged↗

Comparing PSA outcome after radical prostatectomy or magnetic resonance imaging-guided partial prostatic irradiation in select patients with clinically localized adenocarcinoma of the prostate.

OBJECTIVES: To determine whether high-dose radiation delivered to a subvolume of the prostate gland (peripheral zone) using intraoperative magnetic resonance imaging-guided brachytherapy provided comparable 5-year prostate-specific antigen (PSA) control rates to radical prostatectomy (RP) in select patients compared prospectively but in a nonrandomized setting. METHODS: Between 1997 and 2002, 322 and 196 patients with clinical Stage T1c, PSA less than 10 ng/mL, biopsy Gleason score 3 + 4 or less, and without perineural invasion underwent RP or intraoperative magnetic resonance imaging-guided brachytherapy, respectively, and had a 2-year minimal follow-up. Cox regression multivariable analysis was used to evaluate whether the initial therapy, pretreatment PSA level, biopsy Gleason score, percentage of positive biopsies, or prostate gland volume were predictors of the time to post-therapy PSA failure. PSA failure was estimated using the Kaplan-Meier method and defined using the American Society for Therapeutic Radiology Oncology consensus definition. RESULTS: Only the percentage of positive prostate biopsies (P(Cox) = 0.02) was a significant predictor of the time to post-treatment PSA failure. However, the distribution of this parameter between RP and brachytherapy-treated patients was not significantly different (P(chi-square) = 0.25). The initial therapy did not predict for the time to post-therapy PSA failure (P(Cox) = 0.18). The 5-year estimate of PSA control was 93% versus 95% (P(log-rank) = 0.16) for the RP and brachytherapy patients, respectively. CONCLUSIONS: Despite only partial prostatic irradiation using intraoperative magnetic resonance imaging-guided brachytherapy, similar 5-year estimates of PSA control were found for both brachytherapy and RP-managed patients.

Adenocarcinoma↗