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Objective: Single prolonged breath-holds of >5 min can be obtained in cancer patients. Currently, however, the preparation time in each radiotherapy session is a practical limitation for clinical adoption of this new technique. Here, we show by how much our original preparation time can be shortened without unduly compromising breath-hold duration., Methods: 44 healthy subjects performed single prolonged breath-holds from 60% O 2 and mechanically induced hypocapnia. We tested the effect on breath-hold duration of shortening preparation time (the durations of acclimatization, hyperventilation and hypocapnia) by changing these durations and or ventilator settings., Results: Mean original breath-hold duration was 6.5 ± 0.2 (standard error) min. The total original preparation time (from connecting the facemask to the start of the breath-hold) was 26 ± 1 min. After shortening the hypocapnia duration from 16 to 5 min, mean breath-hold duration was still 6.1 ± 0.2 min ( ns vs the original). After abolishing the acclimatization and shortening the hypocapnia to 1 min (a total preparation time now of 9 ± 1 min), a mean breath-hold duration of >5 min was still possible (now significantly shortened to 5.2 ± 0.6 min, p < 0.001). After shorter and more vigorous hyperventilation (lasting 2.7 ± 0.3 min) and shorter hypocapnia (lasting 43 ± 4 s), a mean breath-hold duration of >5 min (5.3 ± 0.2 min, p < 0.05) was still possible. Here, the final total preparation time was 3.5 ± 0.3 min., Conclusions: These improvements may facilitate adoption of the single prolonged breath-hold for a range of thoracic and abdominal radiotherapies especially involving hypofractionation., Advances in Knowledge: Multiple short breath-holds improve radiotherapy for thoracic and abdominal cancers. Further improvement may occur by adopting the single prolonged breath-hold of >5 min. One limitation to clinical adoption is its long preparation time. We show here how to reduce the mean preparation time from 26 to 3.5 min without compromising breath-hold duration.

Objective: To compare bone marrow oedema-like lesion (BML) volume in subjects with symptomatic patellofemoral (PF) knee osteoarthritis (OA) using four different MRI sequences and to determine reliability of BML volume assessment using these sequences and their correlation with pain., Methods: 76 males and females (mean age 55.8 years) with symptomatic patellofemoral knee OA had 1.5 T MRI scans. PD fat suppressed (FS), STIR, contrast-enhanced (CE) T 1 W FS, and 3D T 1 W fast field echo (FFE) sequences were obtained. All sequences were assessed by one reader, including repeat assessment of 15 knees using manual segmentation and the measurements were compared. We used random-effects panel linear regression to look for differences in the log-transformed BML volume (due to positive skew in the BML volume distribution) between sequences and to determine associations between BML volumes and knee pain., Results: 58 subjects had PF BMLs present on at least one sequence. Median BML volume measured using T 1 W FFE sequence was significantly smaller (224.7 mm 3 , interquartile range [IQR] 82.50-607.95) than the other three sequences. BML volume was greatest on the CE sequence (1129.8 mm 3 , IQR 467.28-3166.02). Compared to CE sequence, BML volumes were slightly lower when assessed using PDFS (proportional difference = 0.79; 95% confidence interval [CI] 0.62, 1.01) and STIR sequences (proportional difference = 0.85; 95% CI 0.67, 1.08). There were strong correlations between BML volume on PDFS, STIR, and CE T 1 W FS sequences (ρ s = 0.98). Correlations were lower between these three sequences and T 1 W FFE (ρ s = 0.80-0.81). Intraclass correlation coefficients were excellent for proton density fat-suppressed, short-tau inversion recovery, and CE T 1 W FS sequences (0.991-0.995), while the ICC for T 1 W FFE was good at 0.88. We found no significant association between BML volumes assessed using any of the sequences and knee pain., Conclusion: T 1 W FFE sequences were less reliable and measured considerably smaller BML volume compared to other sequences. BML volume was larger when assessed using the contrast enhanced T 1 W FS though not statistically significantly different from BMLs when assessed using PDFS and STIR sequences., Advances in Knowledge: This is the first study to assess BMLs by four different MRI pulse sequences on the same data set, including different fluid sensitive sequences and gradient echo type sequence.

Objective: Multiple, short and deep inspiratory breath-holds with air of approximately 20 s are now used in radiotherapy to reduce the influence of ventilatory motion and damage to healthy tissue. There may be further clinical advantages in delivering each treatment session in only one single, prolonged breath-hold. We have previously developed techniques enabling healthy subjects to breath-hold for 7 min. Here, we demonstrate their successful application in patients with cancer., Methods: 15 patients aged 37-74 years undergoing radiotherapy for breast cancer were trained to breath-hold safely with pre-oxygenation and mechanically induced hypocapnia under simulated radiotherapy treatment conditions., Results: The mean breath-hold duration was 5.3 ± 0.2 min. At breakpoint, all patients were normocapnic and normoxic [mean end-tidal partial pressure of carbon dioxide was 36 ± 1 standard error millimetre of mercury, (mmHg) and mean oxygen saturation was 100 ± 0 standard error %]. None were distressed, nor had gasping, dizziness or disturbed breathing in the post-breath-hold period. Mean blood pressure had risen significantly from 125 ± 3 to 166 ± 4 mmHg at breakpoint (without heart rate falling), but normalized within approximately 20 s of the breakpoint. During breath-holding, the mean linear anteroposterior displacement slope of the L breast marker was <2 mm min(-1)., Conclusion: Patients with cancer can be trained to breath-hold safely and under simulated radiotherapy treatment conditions for longer than the typical beam-on time of a single fraction. We discuss the important applications of this technique for radiotherapy., Advances in Knowledge: We demonstrate for the first time a technique enabling patients with cancer to deliver safely a single prolonged breath-hold of >5 min (10 times longer than currently used in radiotherapy practice), under simulated radiotherapy treatment conditions.

Objective: Variability in the breathing pattern of patients with cancer during radiotherapy requires mitigation, including enlargement of the planned treatment field, treatment gating and breathing guidance interventions. Here, we provide the first demonstration of how easy it is to mechanically ventilate patients with breast cancer while fully conscious and without sedation, and we quantify the resulting reduction in the variability of breathing., Methods: 15 patients were trained for mechanical ventilation. Breathing was measured and the left breast anteroposterior displacement was measured using an Osiris surface-image mapping system (Qados Ltd, Sandhurst, UK)., Results: Mechanical ventilation significantly reduced the within-breath variability of breathing frequency by 85% (p < 0.0001) and that of inflation volume by 29% (p < 0.006) when compared with their spontaneous breathing pattern. During mechanical ventilation, the mean amplitude of the left breast marker displacement was 5 ± 1 mm, the mean variability in its peak inflation position was 0.5 ± 0.1 mm and that in its trough inflation position was 0.4 ± 0.0 mm. Their mean drifts were not significantly different from 0 mm min(-1) (peak drift was -0.1 ± 0.2 mm min(-1) and trough drift was -0.3 ± 0.2 mm min(-1)). Patients had a normal resting mean systolic blood pressure (131 ± 5 mmHg) and mean heart rate [75 ± 2 beats per minute (bpm)] before mechanical ventilation. During mechanical ventilation, the mean blood pressure did not change significantly, mean heart rate fell by 2 bpm (p < 0.05) with pre-oxygenation and rose by only 4 bpm (p < 0.05) during pre-oxygenation with hypocapnia. No patients reported discomfort and all 15 patients were always willing to return to the laboratory on multiple occasions to continue the study., Conclusion: This simple technique for regularizing breathing may have important applications in radiotherapy., Advances in Knowledge: Variations in the breathing pattern introduce major problems in imaging and radiotherapy planning and delivery and are currently addressed to only a limited extent by asking patients to breathe to auditory or visual guidelines. We provide the first demonstration that a completely different technique, of using a mechanical ventilator to take over the patients' breathing for them, is easy for patients who are conscious and unsedated and reduces the within-patient variability of breathing. This technique has potential advantages in radiotherapy over currently used breathing guidance interventions because it does not require any active participation from or feedback to the patient and is therefore worthy of further clinical evaluation.

Objective: While there is recent interest in using repeated deep inspiratory breath-holds, or prolonged single breath-holds, to improve radiotherapy delivery, breath-holding has risks. There are no published guidelines for monitoring patient safety, and there is little clinical awareness of the pronounced blood pressure rise and the potential for gradual asphyxia that occur during breath-holding. We describe the blood pressure rise during deep inspiratory breath-holding with air and test whether it can be abolished simply by pre-oxygenation and hypocapnia., Methods: We measured blood pressure, oxygen saturation (SpO2) and heart rate in 12 healthy, untrained subjects performing breath-holds., Results: Even for deep inspiratory breath-holds with air, the blood pressure rose progressively (e.g. mean systolic pressure rose from 133 ± 5 to 175 ± 8 mmHg at breakpoint, p < 0.005, and in two subjects, it reached 200 mmHg). Pre-oxygenation and hypocapnia prolonged breath-hold duration and prevented the development of asphyxia but failed to abolish the pressure rise. The pressure rise was not a function of breath-hold duration and was not signalled by any fall in heart rate (remaining at resting levels of 72 ± 2 beats per minute)., Conclusion: Colleagues should be aware of the progressive blood pressure rise during deep inspiratory breath-holding that so far is not easily prevented. In breast cancer patients scheduled for breath-holds, we recommend routine screening for heart, cardiovascular, renal and cerebrovascular disease, routine monitoring of patient blood pressure and SpO2 during breath-holding and requesting patients to stop if systolic pressure rises consistently >180 mmHg and or SpO2 falls <94%., Advances in Knowledge: There is recent interest in using deep inspiratory breath-holds, or prolonged single breath-holding techniques, to improve radiotherapy delivery. But there appears to be no clinical awareness of the risks to patients from breath-holding. We demonstrate the progressive blood pressure rise during deep inspiratory breath-holds with air, which we show cannot be prevented by the simple expedient of pre-oxygenation and hypocapnia. We propose patient screening and safety guidelines for monitoring both blood pressure and SpO2 during breath-holds and discuss their clinical implications.