Geoffrey Charles-Edwards

Radiotherapy treatment planning of prostate cancer using magnetic resonance imaging alone

PURPOSE Accurate anatomical delineation of the gross tumour volume (GTV) is crucial for effective radiotherapy (RT) treatment of prostate cancers. Although reference to pelvic magnetic resonance (MR) for improved delineation of the prostate is a regular practice in some clinics, MR has not replaced CT due to its geometrical distortions and lack of electron-density information. The possibility and practicality of using MR only for RT treatment planning were studied. MATERIALS AND METHODS The addition of electron-density information to MR images for conformal radiotherapy (CRT) planning of the prostate was quantified by comparing dose distributions created on the homogeneous density- and bulk-density assigned images to original CT for four patients. To quantify the MR geometrical distortions measurements of a phantom imaged in CT (Siemens Somatom Plus 4) and FLASH 3D T1-weighted MR (1.5 T whole body Siemens Magnetom Vision) were compared. Dose statistics from CRT treatment plans made on CT and MR for five patient data were compared to determine if MR-only treatment plans can be made. RESULTS The differences between dose-plans on bulk-density assigned images when compared to CT were less than 2% when water and bone values were assigned. Dose differences greater than 2% were observed when images of homogeneous-density assignment were compared to the CT. Phantom measurements showed that the distortions in the FLASH 3D T1-weighted MR averaged 2 mm in the volume of interest for prostate RT planning. For the CT and MR prostate planning study, doses delivered to the planning target volume (PTV) in CT and MR were always inside a 93-107% dose range normalised to the isocentre. Also, the doses to the organs-at-risk in the MR images were similar to the doses delivered to the volumes in the registered CT image when the organ volumes between the two images were similar. CONCLUSIONS Negligible differences were observed in dose distribution between CRT plans using bone+water CT number bulk-assigned image and original CT. Also, the MR distortions were reduced to negligible amounts using large bandwidth MR sequence for prostate CRT planning. MR treatment planning was demonstrated using a large bandwidth sequence and bulk-assigned images. The development of higher quality, low distortion MR sequence will allow regular practice of this technique.

Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial

Summary Background Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Methods Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36–43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. Findings The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference −0·01, 95% CI −0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. Interpretation Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia. Funding UK Medical Research Council.

Changes in Primary Breast Cancer Heterogeneity May Augment Midtreatment MR Imaging Assessment of Response to Neoadjuvant Chemotherapy

PURPOSE To evaluate whether changes in magnetic resonance (MR) imaging heterogeneity may aid assessment for pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in primary breast cancer and to compare pCR with standard Response Evaluation Criteria in Solid Tumors response. MATERIALS AND METHODS Institutional review board approval, with waiver of informed consent, was obtained for this retrospective analysis of 36 consecutive female patients, with unilateral unifocal primary breast cancer larger than 2 cm in diameter who were receiving sequential anthracycline-taxane NACT between October 2008 and October 2012. T2- and T1-weighted dynamic contrast material-enhanced MR imaging was performed before, at midtreatment (after three cycles), and after NACT. Changes in tumor entropy (irregularity) and uniformity (gray-level distribution) were determined before and after MR image filtration (for different-sized features). Entropy and uniformity for pathologic complete responders and nonresponders were compared by using the Mann-Whitney U test and receiver operating characteristic analysis. RESULTS With NACT, there was an increase in uniformity and a decrease in entropy on T2-weighted and contrast-enhanced subtracted T1-weighted MR images for all filters (uniformity: 23.45% and 22.62%; entropy: -19.15% and -19.26%, respectively). There were eight complete pathologic responders. An area under the curve of 0.84 for T2-weighted MR imaging entropy and uniformity (P = .004 and .003) and 0.66 for size (P = .183) for pCR was found, giving a sensitivity and specificity of 87.5% and 82.1% for entropy and 87.5% and 78.6% for uniformity compared with 50% and 82.1%, respectively, for tumor size change for association with pCR. CONCLUSION Tumors become more homogeneous with treatment. An increase in T2-weighted MR imaging uniformity and a decrease in T2-weighted MR imaging entropy following NACT may provide an earlier indication of pCR than tumor size change.

Measurements of occupational exposure to switched gradient and spatially‐varying magnetic fields in areas adjacent to 1.5T clinical MRI systems

To determine if magnetic field exposure close to two clinical 1.5T magnetic resonance imaging (MRI) scanners during image acquisition and when moving in the spatially‐varying static magnetic field is compliant with European Union (EU) Directive 2004/40/EC (the Directive).

Performance Evaluation of an MRI-Compatible Pre-Clinical PET System Using Long Optical Fibers

We have designed and constructed an MR-compatible PET system for fully simultaneous PET/MR studies of small animals. The scanner uses long optical fibers to distance the magnetic field sensitive PET PMTs from the high magnetic field at the center of an MR scanner. It is a single slice system with an inner diameter of 7 cm. A full evaluation of the performance of the PET system and the results of an MR compatibility assessment in a Philips Achieva whole body 3 T MRI scanner are presented. The reconstructed resolution of the PET scanner is 1.5 mm at the center falling to 2.5 mm at the edge of the field of view; the system sensitivity is 0.95%; the count rate is linear up to an activity of 6 MBq (~4 kcps) and the scatter fraction is 42% which can be reduced to 26% using MR-compatible gamma shields. Simultaneous PET/MR images of phantoms and a mouse have been acquired. The system is highly MR compatible, as demonstrated here, showing no degradation in performance of either the MR or PET system in the presence of the other modality. The system will be used to demonstrate novel pre-clinical applications of simultaneous PET/MR.

Non-invasive detection and quantification of human foetal brain lactate in utero by magnetic resonance spectroscopy.

To assess the feasibility of foetal cerebral lactate detection and quantification by proton magnetic resonance spectroscopy (1H‐MRS) in pregnancies at increased risk of cerebral hypoxia, using a clinical 1.5 T magnetic resonance imaging (MRI) system.

Observation and Modeling of Deep Brain Stimulation Electrode Depth in the Pallidal Target of the Developing Brain

OBJECTIVE It is unclear how brain growth with age affects electrode position in relation to target for children undergoing deep brain stimulation surgery. We aimed to model projected change in the distance between the entry point of the electrode into the brain and target during growth to adulthood. METHODS Modeling was performed using a neurodevelopmental magnetic resonance imaging database of age-specific templates in 6-month increments from 4 to 18 years of age. Coordinates were chosen for a set of entry points into both cerebral hemispheres and target positions within the globus pallidus internus on the youngest magnetic resonance imaging template. The youngest template was nonlinearly registered to the older templates, and the transformations generated by these registrations were applied to the original coordinates of entry and target positions, mapping these positions with increasing age. Euclidean geometry was used to calculate the distance between projected electrode entry and target with increasing age. RESULTS A projected increase in distance between entry point and target of 5-10 mm was found from age 4 to 18 years. Most change appeared to occur before 7 years of age, after which minimal change in distance was found. CONCLUSIONS Electrodes inserted during deep brain stimulation surgery are tethered at the point of entry to the skull. Brain growth, which could result in a relative retraction with respect to the original target position, appears to occur before 7 years of age, suggesting careful monitoring is needed for children undergoing implantation before this age. Reengineering of electrode design could avoid reimplantation surgery in young children undergoing deep brain stimulation.

Rectal tumour volume (GTV) delineation using T2-weighted and diffusion-weighted MRI: Implications for radiotherapy planning.

PURPOSE To compare the rectal tumour gross target volume (GTV) delineated on T2 weighted (T2W MRI) and diffusion weighted MRI (DWI) images by two different observers and to assess if agreement is improved by DWI. MATERIAL AND METHODS 27 consecutive patients (15 male, range 27.1-88.8 years, mean 66.9 years) underwent 1.5T MRI prior to chemoradiation (45Gy in 25 fractions; oral capecitabine 850mg/m(2)), including axial T2W MRI (TR=6600ms, TE=90ms) and DWI (TR=3000ms, TE=77ms, b=0, 100, 800s/mm(2)). 3D tumour volume (cm(3)) was measured by volume of interest (VOI) analysis by two independent readers for the T2W MRI and b800 DWI axial images, and the T2W MRI and DWI volumes compared using Mann-Whitney test. Observer agreement was assessed using Bland-Altman statistics. Significance was at 5%. RESULTS Artefacts precluded DWI analysis in 1 patient. In the remaining 26 patients evaluated, median (range) T2W MRI MRI and DWI (b=800s/mm(2)) 3D GTVin cm(3) were 33.97 (4.44-199.8) and 31.38 (2.43-228), respectively, for Reader One and 43.78 (7.57-267.7) and 42.45 (3.68-251) for Reader Two. T2W MRI GTVs were slightly larger but not statistically different from DWI volumes: p=0.52 Reader One; p=0.92 Reader Two. Interobserver mean difference (95% limits of agreement) for T2W MRI and DWI GTVs were -9.84 (-54.96 to +35.28) cm(3) and -14.79 (-54.01 to +24.43) cm(3) respectively. CONCLUSION Smaller DWI volumes may result from better tumour conspicuity but overall observer agreement is not improved by DWI.

In vitro and in vivo comparison of two-, three- and four-point Dixon techniques for clinical intramuscular fat quantification at 3 T.

OBJECTIVE To compare Dixon-based MRI techniques for intramuscular fat quantification at 3 T with MR spectroscopy (MRS) in vitro and in vivo. METHODS In vitro, two- three- and four-point mDixon (Philips Medical Systems, Best, Netherlands) sequences with 10°, 20° and 30° flip angles were acquired from seven test phantoms with sunflower oil-water percentages of 0-60% sunflower oil and calculated fat-water ratios compared with MRS. In vivo, two- three- and four-point mDixon sequences with 10° flip angle were acquired and compared with MRS in the vastus medialis of nine healthy volunteers (aged 30.6 ± 5.3 years; body mass index 22.2 ± 2.6). RESULTS In vitro, all mDixon sequences correlated significantly with MRS (r > 0.97, p < 0.002). The measured phantom percentage fat depended significantly on the flip angle (p ≤ 0.001) and mDixon sequence (p = 0.005). Flip angle was the dominant factor influencing agreement with MRS. Increasing the flip angle significantly increased the overestimation of the mDixon sequences compared with MRS. In vivo, a significant difference was observed between sequences (p < 0.001), with all mDixon sequences overestimating the intramuscular fat content of the vastus medialis muscle compared with MRS. Two-point mDixon agreed best with MRS and had comparable variability with the other mDixon sequences. CONCLUSION This study demonstrates that mDixon techniques have good linearity and low variability for use in intramuscular fat quantification. To avoid significant fat overestimation with short repetition time, a low flip angle should be used to reduce T1 effects. ADVANCES IN KNOWLEDGE This is the first study investigating the optimal mDixon parameters for intramuscular fat quantification compared with MRS in vivo and in vitro.

Water–fat separation in diffusion-weighted EPI using an IDEAL approach with image navigator

Echo planar‐based diffusion‐weighted MRI (DW‐MRI) requires robust suppression of fat signal. Fat suppression techniques such as inversion recovery or spectrally selective excitation with subsequent gradient spoiling can extend scan time or perform suboptimally in the presence of strong main field inhomogeneities. Chemical shift‐encoded water–fat separation using iterative decomposition of water and fat with echo asymmetry and least‐squares estimation (IDEAL) is robust in areas of main field inhomogeneity but requires accurate phase information, which can be distorted by patient motion during diffusion‐weighting gradients. A method is proposed to overcome this with the use of image navigators.