George P. Topulos

REAL-TIME MAGNETIC RESONANCE IMAGE-GUIDED INTERSTITIAL BRACHYTHERAPY IN THE TREATMENT OF SELECT PATIENTS WITH CLINICALLY LOCALIZED PROSTATE CANCER

PURPOSE This study was performed to establish the dose-localization capability and acute toxicity of a real-time intraoperative magnetic resonance (MR) image-guided approach to prostate brachytherapy in select patients with clinically localized prostate cancer. METHODS AND MATERIALS Nine patients with 1997 American Joint Commission on Cancer (AJCC) clinical stage T1cNxM0 prostate cancer, prostate-specific antigen (PSA) < 10 ng/ml, biopsy Gleason score not exceeding 3 + 4, and endorectal coil MR stage T2 disease were enrolled into this study. The prescribed minimum peripheral dose was 160 Gy to the clinical target volume (CTV), which was the MR-defined peripheral zone (PZ) of the prostate gland. Using a real-time 0.5 Tesla intraoperative MR imaging unit, 5-mm image planes were obtained throughout the prostate gland. The PZ of the prostate gland, anterior rectal wall, and prostatic urethra were identified on the T2 weighted axial images by an MR radiologist. An optimized treatment plan for catheter insertion was generated intraoperatively. Each catheter containing the 125Iodine sources was placed under real-time MR guidance to ensure that its position in the coronal, sagittal, and axial planes was in agreement with the planned trajectory. Real-time dose- volume histogram analyses were used intraoperatively to optimize the dosimetry. RESULTS For the 9 study patients, 89-99% (median 94%) of the CTV received a minimum peripheral dose of 160 Gy and > or = 95% of the volume of the prostatic urethra and 42-89% (median 70%) of the volume of the anterior rectal wall received doses that were below the reported tolerance. All patients voided spontaneously within 3 h after discontinuation of the Foley catheter and no patient required more than a limited course (< or = 3 weeks) of oral alpha-1 blockers for postimplant urethritis. CONCLUSIONS Real-time MR-guided interstitial radiation therapy provided the ability to achieve the planned optimized dose-volume histogram profiles to the CTV and healthy juxtaposed structures intraoperatively, with minimal acute morbidity.

Human pulmonary imaging and spectroscopy with hyperpolarized 129Xe at 0.2T.

RATIONALE AND OBJECTIVES Using a novel (129)Xe polarizer with high throughput (1-2 L/hour) and high polarization (approximately 55%), our objective was to demonstrate and characterize human pulmonary applications at 0.2T. Specifically, we investigated the ability of (129)Xe to measure the alveolar surface area per unit volume of gas, S(A)/V(gas). MATERIALS AND METHODS Variable spin echo time (TE) gradient and radiofrequency (RF) echoes were used to obtain estimates of the lungs contribution to both T(2)* and T(2). Standard multislice ventilation images were obtained and signal-to-noise ratio (SNR) determined. Whole-lung, time-dependent measurements of (129)Xe diffusion from gas to septal tissue were obtained with a chemical shift saturation recovery (CSSR) method. Four healthy subjects were studied, and the Butler et al CSSR formalism (J Phys Condensed Matter 2002; 14:L297-L304) was used to calculate S(A)/V(gas). A single-breath version of the xenon transfer contrast (SB-XTC) method was implemented and used to image (129)Xe diffusion between alveolar gas and septal tissue. A direct comparison of CSSR and SB-XTC was performed. RESULTS T(2)*=135+/-29 ms amd T(2)=326.2+/-9.5 ms. Maximum SNR=36 for ventilation images from inhalation of 1L 86% (129)Xe and voxel volume =0.225 mL. CSSR analysis showed S(A)/V(gas) decreased with increasing lung volume in a manner very similar to that observed from histology measurements; however, the absolute value of S(A)/V(gas) was approximately 40% smaller than histology values. SB-XTC images in different postures demonstrate gravitationally dependent values. Initial comparison of CSSR with XTC showed fairly good agreement with expected ratios. CONCLUSIONS Hyperpolarized (129)Xe human imaging and spectroscopy are very promising methods to provide functional information about the lung.

Airway changes during labor and delivery.

Background:There are no prospective studies that evaluated airway changes during labor. The purpose of this study was to evaluate airway changes in women undergoing labor and delivery. Methods:Two studies were undertaken to evaluate airway changes during labor. The first study used the conventional Samsoon modification of the Mallampati airway class. The airway was photographed at the onset and the end of labor. Women with class 4 airways were excluded from initial participation. In the second study, upper airway volumes were measured using acoustic reflectometry at the onset and the conclusion of labor. Acoustic reflectometry software computed the values for the components of upper airway, oral volume, and pharyngeal volume. Results:In study 1 (n = 61), there was a significant increase in airway class from prelabor to postlabor (P < 0.001). The airway increased one grade higher in 20 (33%) and two grades higher in 3 (5%) after labor. At the end of labor, there were 8 parturients with airway class 4 (P < 0.01) and 30 parturients with airway class 3 or class 4 (P < 0.001). In study 2 (n = 21), there were significant decreases in oral volume (n = 21; P < 0.05), and pharyngeal area (P < 0.05) and volume (P < 0.001) after labor and delivery. No correlation was observed between airway changes during labor and duration of labor, or fluids administered during labor in either study. Conclusion:Airways can change during labor. Therefore, a careful airway evaluation is essential just before administering anesthesia during labor rather than obtaining this information from prelabor data.

Image-Guided Surgery in a New Magnetic Resonance Suite: Preclinical Considerations†‡

Surgical procedures require correct identification of exposed anatomy with concomitant localization amidst contiguous structures. In endoscopic procedures the surgeon is provided a real‐time endoscopic view and is prepared with radiologic images. Here we present an overview of a methodology of localization using intraoperatively acquired magnetic resonance(MR) images in preparation for magnetic resonance imaging‐guided endoscopic sinus surgery. The methodology centers around a unique prototype imaging device and operating environment. An “open” 0.5 Tesla MR unit has been created that allows complete access to the patients head and neck while concomitant images are obtained. Illustrative examples of the localization technique from cadaver experiments are presented, as well as insights into the host of concerns for anesthesia, equipment, surgical instrumentation, communications, and documentation.

Measuring surface-area-to-volume ratios in soft porous materials using laser-polarized xenon interphase exchange nuclear magnetic resonance

We demonstrate a minimally invasive nuclear magnetic resonance (NMR) technique that enables determination of the surface-area-to-volume ratio (S/V) of soft porous materials from measurements of the diffusive exchange of laser-polarized 129Xe between gas in the pore space and 129Xe dissolved in the solid phase. We apply this NMR technique to porous polymer samples and find approximate agreement with destructive stereological measurements of S/V obtained with optical confocal microscopy. Potential applications of laser-polarized xenon interphase exchange NMR include measurements of in vivo lung function in humans and characterization of gas chromatography columns.

Effect of inhaled furosemide on air hunger induced in healthy humans

Recent evidence suggests that inhaled furosemide relieves dyspnoea in patients and in normal subjects made dyspnoeic by external resistive loads combined with added dead-space. Furosemide sensitizes lung inflation receptors in rats, and lung inflation reduces air hunger in humans. We therefore hypothesised that inhaled furosemide acts on the air hunger component of dyspnoea. Ten subjects inhaled aerosolized furosemide (40 mg) or placebo in randomised, double blind, crossover experiments. Air hunger was induced by hypercapnia (50+/-2 mmHg) during constrained ventilation (8+/-0.9 L/min) before and after treatment, and rated by subjects using a 100 mm visual analogue scale. Subjects described a sensation of air hunger with little or no work/effort of breathing. Hypercapnia generated less air hunger in the first trial at 23+/-3 min after start of furosemide treatment (58+/-11% to 39+/-14% full scale); the effect varied substantially among subjects. The mean treatment effect, accounting for placebo, was 13% of full scale (P=0.052). We conclude that 40 mg of inhaled furosemide partially relieves air hunger within 1h and is accompanied by substantial diuresis.

3He lung imaging in an open access, very-low-field human magnetic resonance imaging system

The human lung and its functions are extremely sensitive to gravity; however, the conventional high‐field magnets used for most laser‐polarized 3He MRI of the human lung restrict subjects to lying horizontally. Imaging of human lungs using inhaled laser‐polarized 3He gas is demonstrated in an open‐access very‐low‐magnetic‐field (<5 mT) MRI instrument. This prototype device employs a simple, low‐cost electromagnet, with an open geometry that allows variation of the orientation of the imaging subject in a two‐dimensional plane. As a demonstration, two‐dimensional lung images were acquired with 4‐mm in‐plane resolution from a subject in two orientations: lying supine and sitting in a vertical position with one arm raised. Experience with this prototype device will guide optimization of a second‐generation very‐low‐field imager to enable studies of human pulmonary physiology as a function of subject orientation. Magn Reson Med 53:745–749, 2005.

Endoscopic sinus surgery with magnetic resonance imaging guidance: Initial patient experience:

We report the first endoscopic surgeries performed with patients under general anesthesia using intraoperative guidance with MRI. The procedures were experimental and intended to test (1) the unusual working environment of a unique new “open-configuration” MRI unit for head and neck surgery, and (2) real-time image guidance. Twelve patients underwent endoscopic sinus surgery while under general anesthesia in a new open MRI unit that provides the surgeon with access to the patient while imaging is performed. Eleven patients had chronic sinusitis (eight of them had bilateral disease), and one had a right nasoethmoid and antral tumor. All 12 surgeries were performed without complications. Both the endoscopic view and the MRI scans were available at the surgical field. The image plane was surgeon controlled, and the MRI updated images in as little as 14 seconds. MRI provided adequate visualization of both the disease and the related anatomy and allowed the surgeon to navigate during the procedure. The intraoperative data reflect the tissue changes during surgery and provide optimum feedback for surgical guidance. Although the operating environment poses some limitations, it has become apparent that intraoperative MRI has a role in the treatment of head and neck disorders and warrants further study.

Acute partial paralysis alters perceptions of air, hunger, work and effort at constant PCO2 and Ve.

Breathing sensations of AIR HUNGER, WORK and EFFORT may depend on projections of central motor discharge (corollary discharge) to the forebrain. Source of motor drive (brainstem or cortex) may determine what is perceived. To test the effect of changing motor discharge at constant ventilation, we induced partial neuromuscular blockade during hypercapnic hyperpnea (31 + or - 9 L min(-1); PET(CO(2))=49 + or - 2 Torr) and during matched volitional hyperpnea (34 + or - 5 L min(-1); PET(CO(2))=41 + or - 1 Torr). Decline of vital capacity was similar between conditions (39%). Ventilation was unchanged with paralysis, indicating increased respiratory motor drive to maintain hyperpnea. Sensations were rated on a seven point ordinal scale. Median EFFORT and WORK increased 3-3.5 points with paralysis during both forms of hyperpnea (P<0.02, Wilcoxon signed rank). Median AIR HUNGER increased 2.5 points with paralysis during hypercapnic (P<0.02) but not during volitional hyperpnea. Data suggests that EFFORT and WORK arise from motor cortex activity (subjects reported engaging volitional control when paralyzed even during hypercapnia) and suggests that AIR HUNGER arises from medullary motor activity.

Hyperthermia combined with radiation in treatment of locally advanced prostate cancer is associated with a favourable toxicity profile

Purpose: Hyperthermia is used to treat several pelvic tumours. An important step in establishing a broader role for hyperthermia in treatment of prostate cancer is verification of an acceptable toxicity profile. In this report, short- and long-term toxicity profiles of a completed phase II trial of transrectal ultrasound hyperthermia combined with radiation in treatment of locally advanced prostate cancer are presented. Methods and materials: Thirty-seven patients enrolled on a phase II study of external beam radiation ± androgen suppression with two transrectal ultrasound hyperthermia treatments were assessed for short- and long-term toxicity. Prostatic and anterior rectal wall temperatures were monitored. Rectal wall temperatures were limited to 40°C (19 patients), 41°C (three patients) and 42°C (15 patients). Univariate logistic regression was used to estimate the log hazard of developing NCI CTC Grade 2 toxicity based on temperature parameters. Hazard ratios, 95% confidence intervals, p-values for statistical significance of each parameter and proportion of variability explained for each of the parameters were calculated. Results: Median follow-up was 42 months. Both short- and long-term GI toxicity were limited to grade 2 or less. Acute grade 2 proctitis was greater for patients with allowable rectal wall temperature of >40°C. Eleven of 18 patients in this group had acute grade 2 proctitis vs three of 19 patients with rectal wall temperatures limited to 40°C (p = 0.004). Long-term grade 2 GI and GU toxicity occurred in 5% and 19% of patients. No late grade 3 or greater toxicity occurred. Late GI and GU toxicity were not associated with the allowable rectal wall temperature. Conclusion: Transrectal ultrasound hyperthermia combined with radiation for treatment of advanced clinically localized prostate cancer is safe and well tolerated.