The feasibility of CT simulation-free adaptive radiation therapy.

BACKGROUND: Novel on-board CBCT allows for improved image quality and Hounsfield unit accuracy. When coupled with online adaptive tools, this may have potential to allow for simulation and treatment to be completed in a single on-table session. PURPOSE: To study the feasibility of a high-efficiency radiotherapy treatment workflow without the use of a separate session for simulation imaging. The dosimetric accuracy, overall efficiency, and technical feasibility were used to evaluate the clinical potential of CT simulation-free adaptive radiotherapy. METHODS: Varian's Ethos adaptive radiotherapy treatment platform was upgraded with a novel CBCT system, HyperSight which reports image quality and Hounsfield unit accuracy specifications comparable to standard fan-beam CT. Using in-house developed MATLAB software, CBCT images were imported into the system and used for planning. Two test cases were completed on anthropomorphic phantoms equipped with small volume ion chambers (cross-calibrated to an ADCL traceable dose standard) to evaluate the feasibility and accuracy of the workflows. A simulated palliative spine treatment was planned with 8 Gy in one fraction, and an intact prostate treatment was planned with 60 Gy in 20 fractions. The CBCTs were acquired using HyperSight with default thorax and pelvis imaging protocols and reconstructed using an iterative algorithm with scatter removal, iCBCT Acuros. CBCTs were used for contouring and planning, and treatment was delivered via an online adaptive workflow. In addition, an external dosimetry audit was completed using only on-board CBCT imaging in an end-to-end head and neck phantom irradiation. RESULTS: An extended-field CBCT acquisition can be acquired in 12 s, in addition to the time for longitudinal table shifts, and reconstructed in approximately 1 min. The superior-inferior extent for the CBCT planning images was 38.2 cm, which captured the full extent of relevant anatomy. The contouring and treatment planning for the spine and prostate were completed in 30 and 18 min, respectively. The dosimetric agreement between ion chamber measurements and the treatment plan was within a range of -1.4 to 1.6%, and a mean and standard deviation of 0.41 ± 1.16%. All metrics used in the external audit met the passing criteria, and the dosimetric comparison between fan-beam and CBCT techniques had a gamma passing rate of 99.0% with a criteria of 2%/2 mm. CONCLUSION: Using an in-house workflow, CT simulation-free radiation therapy was shown to be feasible with acceptable workflow efficiency and dosimetric accuracy. This approach may be particularly applicable for urgent palliative treatments. With the availability of software to enable this workflow, and the continued advancement of on-treatment adaptation, single-visit radiation therapy may replace current practice for some clinical indications.

Assessing the impact of intrafraction motion correction on PTV margins and target and OAR dosimetry for single-fraction free-breathing lung stereotactic body radiation therapy.

The objective of this research is to investigate intrafraction motion correction on planning target volume (PTV) margin requirements and target and organ-at-risk (OAR) dosimetry in single-fraction lung stereotactic body radiation therapy (SBRT). Sixteen patients (15 with upper lobe lesions, 1 with a middle lobe lesion) were treated with single-fraction lung SBRT. Cone-beam computed tomography (CBCT) images were acquired before the treatment, between the arcs, and after the delivery of the treatment fraction. Shifts from the reference images were recorded in anterior-posterior (AP), superior-inferior (SI), and lateral (LAT) dimensions. The deviations from the reference image were calculated for 3 clinical scenarios: not applying intratreatment couch shifts and not correcting for pretreatment deviations < 3 mm ( scenario 1), not applying intratreatment couch shifts and correcting for pretreatment deviations < 3 mm ( scenario 2), and applying all pre- and intratreatment couch shifts (scenario 3). PTV margins were determined using the van Herk formalism for each scenario and maximum and average deviations were assessed. The clinical scenarios were modelled in the treatment planning system based on each patient dataset to assess target and OAR dosimetry. Calculated lower-bound PTV margins in the AP, SI, and LAT dimensions were [4.6, 3.5, 2.3] mm in scenario 1, [4.6, 2.4, 2.2] mm in scenario 2, and [1.7, 1.2, 1.0] mm in scenario 3. The margins are lower bounds because they do not include contributions from nonmotion related errors. Average and maximum intrafraction deviations were larger in the AP dimension compared to the SI and LAT dimensions for all scenarios. A unidimensional movement (several mm) in the negative AP dimension was observed in clinical scenarios 1 and 2 but not scenario 3. Average intrafraction deviation vectors were 1.2, 1.1, and 0.3 mm for scenarios 1, 2, and 3, respectively. Modelled clinical scenarios revealed that using scenario 3 yields significantly fewer treatment plan objective failures compared to scenarios 1 and 2 using a Wilcoxon signed-rank test. Intratreatment motion correction between each arc may enable reductions PTV margin requirements. It may also compensate for unidimensional negative AP movement, and improve target and OAR dosimetry.

Resolving the omega-3 methyl resonance with long echo time magnetic resonance spectroscopy in mouse adipose tissue at 9.4 T.

Tissue omega-3 (ω-3) content is biologically important to disease; however, its quantification with magnetic resonance spectroscopy in vivo is challenging due to its low concentration. In addition, the ω-3 methyl resonance (≈ 0.98 ppm) overlaps that of the non-ω-3 (≈ 0.90 ppm), even at 9.4 T. We demonstrate that a Point-RESolved Spectroscopy (PRESS) sequence with an echo time (TE) of 109 ms resolves the ω-3 and non-ω-3 methyl peaks at 9.4 T. Sequence efficacy was verified on five oils with differing ω-3 fat content; the ω-3 content obtained correlated with that measured using 16.5 T NMR (R2 = 0.97). The PRESS sequence was also applied to measure ω-3 content in visceral adipose tissue of three different groups (all n = 3) of mice, each of which were fed a different 20% w/w fat diet. The fat portion of the diet consisted of low (1.4%), medium (9.0%) or high (16.4%) ω-3 fat. The sequence was also applied to a control mouse fed a standard chow diet (5.6% w/w fat, which was 5.9% ω-3). Gas chromatography (GC) analysis of excised tissue was performed for each mouse. The ω-3 fat content obtained with the PRESS sequence correlated with the GC measures (R2 = 0.96). Apparent T2 times of methyl protons were assessed by obtaining spectra from the oils and another group of four mice (fed the high ω-3 diet) with TE values of 109 and 399 ms. Peak areas were fit to a mono-exponentially decaying function and the apparent T2 values of the ω-3 and non-ω-3 methyl protons were 906 ± 148 and 398 ± 78 ms, respectively, in the oils. In mice, the values were 410 ± 68 and 283 ± 57 ms for ω-3 and non-ω-3 fats, respectively.

Long TE PRESS and STEAM for measuring the triglyceride glycerol CH2 protons at 3 T.

The glycerol methylene proton resonances (4-4.5 parts per million, ppm), which arise from the triglyceride backbone, are relevant to fat composition assessment and can be measured with proton MRS. The purpose of the presented work is to determine long TE (echo time) point resolved spectroscopy (PRESS) and stimulated echo acquisition mode (STEAM) values at 3 T to resolve the glycerol resonances from that of overlapping water. The response of the glycerol methylene protons of nine edible oils as a function of PRESS and STEAM TE (mixing time, TM = 20 ms) was investigated. In addition, high resolution NMR spectra of the oils were acquired at 16.5 T. Long TE values where J-coupling losses were lowest were selected, namely a TE of 180 ms for PRESS (first echo time 17 ms) and a TE of 100 ms for STEAM (mixing time 20 ms). Oil olefinic (≈5.4 ppm) to glycerol ratios were calculated from the long TE spectra and correlated with 16.5 T ratios. The two techniques yielded olefinic/glycerol ratios that correlated with 16.5 T ratios (R2  = 0.79 for PRESS and 0.90 for STEAM). The efficacy of the sequences in resolving the glycerol resonance from that of water was verified in vivo on tibial bone marrow of four healthy volunteers. In addition, the potential for using the glycerol methylene signal normalized to the methyl signal (≈0.9 ppm) to assess changes in free fatty acid content was demonstrated by measuring differences in spectra acquired from a triglyceride peanut oil phantom and from a phantom composed of a mixture of peanut oil and free fatty acid oleic acid.

Long TE STEAM and PRESS for estimating fat olefinic/methyl ratios and relative ω-3 fat content at 3T.

BACKGROUND: Fat olefinic/methyl ratios provide a measure of fat unsaturation. The methyl resonance linewidth is altered with the presence of ω-3 fat. PURPOSE: To optimize stimulated echo acquisition mode (STEAM) and point resolved spectroscopy (PRESS) echo times (TE) at 3T to 1) improve olefinic/methyl ratios and 2) enable relative ω-3 fat content assessment. STUDY TYPE: Technical development on phantoms and healthy volunteers. POPULATION: Nine edible oils and four healthy volunteers (tibial bone marrow). FIELD STRENGTH/SEQUENCE: STEAM (mixing time = 20 msec) and PRESS sequences at 3T. High-resolution oil spectra at 16.5T. ASSESSMENT: 3T STEAM and PRESS olefinic/methyl ratios as a function of TE were compared to 16.5T measures for the oils, and to a literature-deduced value for tibial bone marrow. Oil methyl linewidths were calculated at each TE to investigate correlation with expected ω-3 fatty acid content. STATISTICAL TESTS: Percent differences were calculated between oil olefinic/methyl ratios obtained at 3T and 16.5T. Linear regression R2 values measured correlation of methyl linewidth to ω-3 content. RESULTS: STEAM, TE = 120 msec, resulted in average oil olefinic/methyl ratios that differ by about -4.8% compared to high-resolution ratios. Tibial bone marrow olefinic/methyl ratios differ by -1.8% compared with literature-obtained ratios. PRESS, TE = 180 msec, resulted in oil ratios that differ by 7.8% and tibial bone marrow ratios that differ by 0.2%. A TE of 160 msec for both STEAM and PRESS enabled relative levels of oil ω-3 fatty acid content to be estimated (R2 values ≥0.9). DATA CONCLUSION: STEAM, TE = 120 msec (mixing time = 20 msec), and PRESS, TE = 180 msec, optimally estimated olefinic/methyl ratios. STEAM and PRESS, TE = 160 msec, enable relative oil ω-3 fatty acid estimation from methyl linewidths. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2017.