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Biomedical subjects

P Mansfield

Publications and source records attributed to P Mansfield.

At least 19 recordsLinked to original sources

Sound generation in gradient coil structures for MRI.

When supporting plates of plastic material are subjected to alternating transverse Lorentz forces while in a strong magnetic field normal to the plate surface, compressional waves within the solid produce a modulation of the plate surface that launches an acoustic wave in air along the magnetic field axis. We have extended our previous theory describing this process to include a detailed description of the formation of an acoustic interference pattern in air described by Fraunhofer diffraction at a distance from the plate surface. The extended theory predicts that the observed acoustic signal midpoint and normal to the plate surface gives a variation with frequency in approximate agreement with our previous measurements. The acoustic output off axis shows acoustic blazing that produces two main diffraction peaks with a splitting inversely proportional to the velocity of sound in the plate material. The new results could have important ramifications for the minimization of sound output in gradient coil design for MRI. A new arrangement of coils is proposed to ameliorate the acoustic output problem centrally and normal to the plate by extending the frequency response of the supporting plates to much higher frequencies. Also presented are estimates of the compressional wave velocities deduced from frequency response data recorded at the center-point of a number of different plates.

Magnetic Resonance Imaging

Optimization of the ultrafast Look-Locker echo-planar imaging T1 mapping sequence.

The Look-Locker echo-planar imaging (LL-EPI) sequence has been numerically optimized in terms of the signal-to-noise ratio in the measured value of T1, for both single-shot (repetition time (TR) = infinity), and dynamically repeated T1 measurements. The sequence is optimized for the normal biologic range of T1 (0.2 s to 2.0 s) and for a range of sequence parameters found on most magnetic resonance (MR) scanners. Both linearly and geometrically spaced magnetization sample pulse intervals were considered. For single-shot measurements, the sequence with 24 linearly spaced sample pulses, an inversion time of 0.01 s, an inter-sample pulse delay of 0.10 s, and a sample radiofrequency (RF) pulse flip angle of 25 degrees was found to be optimum. When the number of sample pulses was limited due to hardware limitations, different pulse sequence parameters were indicated. The optimization procedures used are appropriate for any single-shot T1 mapping sequence variant and for any rapid T1 mapping application. The use of an optimized Look-Locker echo-planar imaging sequence is demonstrated by an example of dynamic contrast-enhanced scanning in the brain using fast T1 mapping.

Brain

Phase II study of neoadjuvant concurrent biochemotherapy in melanoma patients with local-regional metastases.

Our results with concurrent biochemotherapy in patients with stage IV melanoma have been encouraging. Based on these data, we conducted a phase II study to determine the clinical and histological response rate to neoadjuvant concurrent biochemotherapy in patients with local-regional metastases of cutaneous melanoma (stage III). A total of 65 patients with biopsy-proven, measurable and potentially resectable local-regional disease (nodal, satellite/in-transit metastases and/or local recurrence) were treated with cisplatin 20 mg/m2 intravenously (i.v.) on days 1 to 4, vinblastine 1.5 mg/m2 i.v. on days 1 to 4, dacarbazine 800 mg/m2 i.v. on day 1 only, interleukin-2 9 MIU/m2 per day i.v. by 96 h continuous infusion on days 1 to 4, and interferon-alpha 2a 5 MU/m2 subcutaneously on days 1 to 5, repeated every 3 weeks. Patients underwent surgery after two to four courses of biochemotherapy. Those with tumour regression after two preoperative courses received two additional postoperative courses. Of the 64 patients assessable for clinical response, 28 (44%) had a partial response. Of the 62 patients whose response was assessed histologically, four (6.5%) had no evidence of viable tumour in the surgical specimen (pathological complete remission, pCR) and 27 (43.5%) had a partial response, giving an overall response rate of 50%. Tumour burden did not correlate with response, although patients who achieved a pCR had a significantly lower tumour burden (P = 0.02). Our phase II study indicates that neoadjuvant biochemotherapy is an active treatment for melanoma patients with local-regional metastases. However, it is unclear if biochemotherapy is more active than chemotherapy alone; phase III randomized trials are ongoing to answer this question in patients with stage IV disease.

Adolescent

Critical analysis of the current American Joint Committee on Cancer staging system for cutaneous melanoma and proposal of a new staging system.

PURPOSE: To critically review the accuracy of the current American Joint Committee on Cancer (AJCC) staging system for cutaneous melanoma and propose a more useful staging system. METHODS: Retrospective evaluation of the published data as well as a reanalysis of the University of Alabama and Sydney Melanoma Unit (UAB/SMU) data bases (n = 4,568) for patients with primary melanoma was performed to examine specifically the impact of level of invasion and ulceration on the prognostic value of tumor thickness. In addition, an overlay graphic technique was used to compare the Kaplan-Meier survival curves of patients with local recurrences, satellites, in-transit metastases, and nodal metastases reported in the literature. RESULTS: Tumor thickness and ulceration remained the most powerful prognostic indicators in patients with stage I and II disease. Level of invasion provided statistically significant prognostic information only in the subgroup of patients with tumor thickness < or = 1 mm, but the absolute 10-year survival differences were small and inconsistent (level II, 95%; level III, 85%; level IV, 89%). The best statistical fit for tumor thickness cutoffs was at 1 versus 2 versus 4 mm. The overlay graphic technique showed that patients who developed satellite lesions or local recurrence had prognoses similar to those of patients with stage III disease. The most important prognostic factor for patients with nodal metastases was number of involved nodes rather than size. CONCLUSION: Our analysis showed that the current AJCC staging system has many inaccuracies that should be modified to conform to published data. On the basis of our analysis and review of the literature, we propose a new and more accurate staging system.

Humans

Echo-volumar imaging (EVI) at 0.5 T: first whole-body volunteer studies.

Improvements in the echo-volumar imaging (EVI) technique and its application in whole-body studies are described. Using an in-house built 0.5 T echo-planar imaging system, complete modulus three-dimensional image data are acquired in 102 ms with real-time display. Hardware limitations have restricted the maximum array size achievable to 64 x 32 x 8 voxels. Representative voxel dimensions are x = 6.0 mm; y = 4.0 mm, and z = 10.0 mm. Results on human volunteers are presented, showing cardiac, liver, and bladder images. Also shown are the first EVI gastric filling and emptying results.

Echo-Planar Imaging

A microscopic model of fluid transport in porous rocks.

NMR measurements of water velocity flowing through two different porous rocks, Bentheimer and Clashach, have been made using the PEPI sequence. Random changes of localised velocity occur in both materials even though the average velocities across the core cross-sections follow Darcy's Law. The velocity distributions are approximately Gaussian and the velocity variance follows a linear relationship with mean velocity as predicted in the stochastic theory of Mansfield and Issa. The origin of the large fluctuations in localised velocity is thought to be hydrodynamic and a detailed theory of intervoxel coupling is presented, which accounts for such behaviour in a coupled voxel array. In this work the intervoxel coupling is restricted to isolated voxel pairs.

Echo-Planar Imaging

Echo-planar microscopy of porous rocks.

A modified version of the echo-planar imaging sequence incorporating multiple 180 degrees RF pulses (PEPI) has been implemented at 11.7 T and used to generate high resolution images of porous solids. By preceding the PEPI sequence with an inversion recovery or flow-encoding sequence, rapid T1, and velocity mapping is possible in the microscopic domain.

Echo-Planar Imaging

Transient flow through porous rocks studied by PEPI.

The transient behaviour of fluid flow through porous rocks is examined using the high speed pi-modified echo-planar imaging technique (PEPI). Spatially resolved flow maps show the change in velocity, as the bulk flow rate is increased or decreased in large steps in the approach to steady state for two sandstone samples of different porosity and permeability. Different rise and fall settling times are observed for these rocks. In addition, the area occupied by significant flow and the variance of the velocity distributions are calculated during the transient state.

Echo-Planar Imaging

Simulating MRI flow maps in porous rocks: a new approach.

The Mansfield and Issa model of voxel pair coupling is extended using electrical circuit simulation to interacting voxel clusters comprising all configurations of contiguous voxels up to and including four voxels. This information is used to simulate flow through porous rock samples by calculating the expected velocity distributions found in porous rocks using the PEPI rapid NMR imaging technique.

Computer Simulation

Structure and behavior in hydrophilic matrix sustained release dosage forms: 4. Studies of water mobility and diffusion coefficients in the gel layer of HPMC tablets using NMR imaging.

PURPOSE: The purpose of this study was to characterise the water mobility in the gel layer of hydrating HPMC tablets. Water mobility in the gel layer of different HPMCs was studied. METHODS: NMR imaging, a non-invasive technique, has been used to measure the spatial distribution of self-diffusion coefficient (SDC) and T2 relaxation times across the gel layer. RESULTS: It has been shown that there is a water mobility gradient across the gel layer of HPMC tablets. Although SDC and T2 relaxation times in the outer parts of the gel layer approached that of free water, in the inner parts they decreased progressively. Water mobility and SDC in the gel layer of different HPMCs appeared to vary with degree of substitution of the polymer and the lowest values were obtained across the gel layer of K4M tablets. CONCLUSIONS: Water mobility varies across the gel layer of hydrating HPMC tablets and it is dependent on the degree of substitution of the polymer.

Chemical Phenomena

Cyclosporin A does not reverse clinical resistance to paclitaxel in patients with relapsed non-Hodgkin's lymphoma.

PURPOSE: Cyclosporin A has been shown to reverse paclitaxel resistance in vitro by inhibiting P-gp function. Therefore, we determined whether addition of cyclosporine to paclitaxel reversed clinical paclitaxel resistance in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients with relapsed NHL were eligible if they had no intervening treatment after failure to respond to paclitaxel (200 mg/m2 over 3 hours), and if they had adequate marrow, renal, and hepatic function, no serious cardiac disease, no CNS involvement, and no antibodies to human immunodeficiency virus-1. A cyclosporin A bolus dose (5 mg/kg over 3 hours) was followed by intravenous infusion (15 mg/kg) over 24 hours. Six hours after the beginning of cyclosporin A, the immediately preceding paclitaxel dose was administered over 3 hours. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Response was assessed after two cycles, and those patients who achieved at least a partial response received a maximum of six courses. RESULTS: All 26 patients entered were assessable for toxicity and 25 were assessable for response. One patient whose disease had progressed during paclitaxel treatment had a partial remission after the addition of cyclosporin A (response rate, 4%; 95% confidence interval, 1% to 20%). Disease progressed in 17 patients (71%) and did not respond in seven (25%). Serum cyclosporin A A levels measured at the time of initiation of paclitaxel infusion were greater than 2,000 ng/mL during 81% of cycles. Treatment toxicity included peripheral neuropathy in 57%, myalgia or arthralgia in 30%, neutropenia in 53%, neutropenic fever in 8%, and thrombocytopenia in 42% of patients. One patient with preexisting asthma had an acute bronchospasm during the first cycle and was removed from the study. There were no renal or hepatic toxicity and no infectious or hemorrhagic deaths. CONCLUSION: Cyclosporin A administered on this schedule did not reverse established clinical resistance to paclitaxel, which suggests that P-gp-mediated drug efflux is unlikely to be the only cause of paclitaxel resistance in this patient population.

Adult

Active acoustic screening: reduction of noise in gradient coils by Lorentz force balancing.

We have designed and constructed a quiet gradient set with restricted access for the combined purposes of evaluating the principles of active acoustic screening, recently introduced by Mansfield, Glover, and Bowtell, and for EPI studies of the head at 3.0 T. The design utilizes the return paths of the conductors in a closed arc loop arrangement to eliminate net Lorentz forces thereby attenuating acoustic noise especially at low frequency. This design should significantly reduce the dangers to patients of high noise levels, especially in high field magnetic resonance imaging systems.

Acoustics

NMR microscopy of single neurons using spin echo and line narrowed 2DFT imaging.

NMR microimages of single neural cells were acquired at 500 MHz using a conventional spin echo pulse sequence and a line-narrowing sequence that eliminates susceptibility effects. The data show that any contribution to the measured T2 relaxation rate arising from diffusion in local field inhomogeneities using spin echo sequences at high fields and high spatial resolution is relatively small. We conclude that the measured T2 difference between the nucleus and cytoplasm in these cells represents primarily a true T2 relaxation effect arising from the interactions of water with macromolecules in the two compartments and does not result from microsusceptibility differences. These observations have implications regarding water compartmentation in single cells and the interpretation of the MR characteristics of tissues in vivo.

Animals

Quiet transverse gradient coils: Lorentz force balanced designs using geometrical similitude.

The principle of active acoustic screening, recently introduced by Mansfield et al. (1) to reduce acoustic noise in gradient coils for MRI, is applied to the design of transverse distributed gradient coils of the fingerprint design. The results indicate that for complete Lorentz force balancing and for exact satisfaction of Kirchoff's law, it is necessary to have a coil system wound on four cylinders if full active magnetic screening of the assembly is required.

Magnetic Resonance Imaging

Measurement of fetal liver, brain and placental volumes with echo-planar magnetic resonance imaging.

OBJECTIVE: To quantify accurately in utero fetal liver, brain and placental volumes using echo planar imaging, and to assess whether the technique has the potential to enhance intrauterine fetal assessment. DESIGN: Thirty-two singleton, complicated pregnancies were scanned using echo planar imaging, a form of magnetic resonance imaging. Pregnancies were subdivided on the basis of whether the fetus was found subsequently to have an individualised birthweight ratio above (n = 21) or below (n = 11) the 10th centile. Comparisons of the organ volumes of these two groups were made. RESULTS: The first quantitative in utero measurement of fetal liver volume showed a linear relation between liver volume and gestational age in fetuses where the individualised birthweight ratio was above the 10th centile (the normal growth group). Ten of the 11 liver volume measurements of fetuses subsequently found to have an individualised birthweight ratio below the 10th centile fell on or outside the 95% confidence limits established for the normal growth group. In contrast, no such differences were demonstrated when the brain and placental volumes were considered, with 10 of the 11 brain measurements and all of the 11 placental measurements falling within the 95% confidence limits of the normal growth group. CONCLUSIONS: A single measurement of fetal liver volume using echo planar imaging enabled accurate identification of fetuses subsequently found to have individualised birthweight ratios below the 10th centile. If these findings are repeated in larger, more representative studies, this suggests that the technique has the potential to contribute to intrauterine fetal assessment.

Adult

An assessment of the intrauterine sound intensity level during obstetric echo-planar magnetic resonance imaging.

In order to assess the sound level experienced by the fetal ear during obstetric magnetic resonance imaging, a fluid filled stomach was used as an experimental model of the gravid uterus. A better than 30 dB attenuation in intensity was recorded across the frequency band of interest for all patient orientations. This was enough to reduce acoustic sound pressure from a level close to the instantaneous damage threshold (120 dB), to an acceptable level (< 90 dB). Direct mechanical coupling through the patient table was also shown to increase uterine sound pressure levels by as much as 10 dB. Much higher peak pressures could be obtained by tapping of abdomen with the fingers.

Acoustics