Irregular Breathing Research Articles

Lung Clearance Index is Increased in Patients with COPD - LCI Measurements in the Daily Routine

Objective: The lung clearance index (LCI), an index of ventilation homogeneity derived from the multiple breath wash out (MBW) of an inert gas, is a lung function test to monitor pulmonary disease. The aim of this study was to investigate whether LCI measurements are suitable for the daily routine in patients with COPD in comparison to young and healthy controls. Methods: MBW measurements were performed successfully in 23 patients (out of 42) patients with COPD (FEV1 %, 40.41 ± 14.65). As controls we selected 30 healthy and young volunteers. All subjects used the EasyOne ProLab™ (ndd, Switzerland). Results: 18 patients were not able to finish measurements successfully because of significant leaks, cough and irregular breathing (GOLD I n=1 (5.6%); GOLD II n=6 (33.3%); GOLD III n=5 (27.7%); GOLD IV n=6 (33.3%). The mean LCI was significantly higher in COPD patients as compared to young and healthy volunteers (12.55 ± 3.50 vs 7.00 ± 1.02, p<0.05). Although LCI correlated with FEV1 %of predicted (r²=-0.540, p<0.01) and Rtot (% pred.) (r²=0.504, p<0.01) the method failed to discriminate between GOLD II-IV classes. LCI correlated with the volume of trapped gas in elderly patients with COPD and young and healthy controls [FRC (% pred.) (r²=0.191, p<0.01), ITGV (% pred.) (r²=0.478, p<0.01), and RV (% pred.) (r²=0.462, p<0.01)]. Moreover, the results did not correlate with the 6-MWT, a validated clinical outcome parameter. Conclusions: Although measurement of LCI was capable to detect inhomogeneous ventilation (airway obstruction and hyperinflation), this method did not discriminate between GOLD II-IV and did not correlate with 6-MWT. More than 43% of the patients with COPD did not complete the study because of difficulties with the method. Nevertheless, the LCI might be a tool to gain insight into lung pathophysiology in younger patients e.g. children. Our preliminary study encourages further investigations for the future.

Target-Matching Accuracy in Stereotactic Body Radiation Therapy of Lung Cancer: An Investigation Based on Four-Dimensional Digital Human Phantom

Aim: To investigate the effect of irregular respiratory on target-matching accuracy in lung stereotactic-body radiation therapy (SBRT). Methods: The four-dimensional extended cardiac torso (4D-XCAT) phantom was used to generate 4D computed tomography (4DCT) and cone-beam CT (CBCT) images. Images were generated for 1 regular and 10 irregular trajectories, and for 3 tumor size groups (1, 2, and 3 cm). Image registrations between CBCT and average intensity projection (AIP) images of 4DCT were performed based on target volume matching. Error of registration was determined as the difference between manual CBCT-to-AIP registration and known registration between the two. In addition, internal target volumes (ITVs) were contoured on and compared between AIP, maximum intensity projection (MIP), and CBCT. Results: Small inter-observer variations of registration were found: 0.2, 0.3, and 0.7 mm in the medial-lateral (ML), anterior-posterior (AP), and superior-inferior (SI) direction, respectively. Small errors of registration (median ≤ 0.5 mm) were found in all three directions for the regular respiratory profile. For the irregular profiles and on average of all tumor size groups, the median ± standard deviation (SD) errors of registration were 0.5 ± 0.3 mm, 0.4 ± 0.5 mm, and 1.9 ± 1.6 mm in the ML, AP, and SI direction, respectively. Significant differences were found between MIP and CBCT-based ITV volumes for the three tumor size groups (P = 0.011, 0.010, and 0.006 for 1, 2, and 3 cm tumor size group, respectively). Conclusion: Irregular breathing can induce error in CBCT-to-AIP registration in lung SBRT. This error increases as the breathing irregularity increases.

Markerless Respiratory Motion Tracking Using Single Depth Camera

The aim of this study is to propose a novel system that has an ability to detect intra-fractional motion during radiotherapy treatment in real-time using three-dimensional surface taken by a depth camera, Microsoft Kinect v1. Our approach introduces three new aspects for three-dimensional surface tracking in radiotherapy treatment. The first aspect is a new algorithm for noise reduction of depth values. Ueda’s algorithm was implemented and enabling a fast least square regression of depth values. The second aspect is an application for detection of patient’s motion at multiple points in thracoabdominal regions. The third aspect is an estimation of three-dimensional surface from multiple depth values. For evaluation of noise reduction by Ueda’s algorithm, two respiratory patterns are measured by the Kinect as well as a laser range meter. The resulting cross correlation coefficients between the laser range meter and the Kinect were 0.982 for abdominal respiration and 0.995 for breath holding. Moreover, the mean cross correlation coefficients between the signals of our system and the signals of Anzai with respect to participant’s respiratory motion were 0.90 for thoracic respiration and 0.93 for abdominal respiration, respectively. These results proved that the performance of the developed system was comparable to existing motion monitoring devices. Reconstruction of three-dimensional surface also enabled us to detect the irregular motion and breathing arrest by comparing the averaged depth with predefined threshold values.

Deficiency of GABAergic synaptic inhibition in the Kölliker-Fuse area underlies respiratory dysrhythmia in a mouse model of Rett syndrome.

Life threatening breathing irregularity and central apnoeas are highly prevalent in children suffering from Rett syndrome. Abnormalities in inhibitory synaptic transmission have been associated with the physiopathology of this syndrome, and may underlie the respiratory disorder. In a mouse model of Rett syndrome, GABAergic terminal projections are markedly reduced in the Kölliker-Fuse nucleus (KF) in the dorsolateral pons, an important centre for control of respiratory rhythm regularity. Administration of a drug that augments endogenous GABA localized to this region of the pons reduced the incidence of apnoea and the respiratory irregularity of Rett female mice. Conversely, the respiratory disorder was recapitulated by blocking GABAergic transmission in the KF area of healthy rats. This study helps us understand the mechanism for generation of respiratory abnormality in Rett syndrome, pinpoints a brain site responsible and provides a clear anatomical target for the development of a translatable drug treatment. Central apnoeas and respiratory irregularity are a common feature in Rett syndrome (RTT), a neurodevelopmental disorder most often caused by mutations in the methyl-CpG-binding protein 2 gene (MECP2). We used a MECP2 deficient mouse model of RTT as a strategy to obtain insights into the neurobiology of the disease and into mechanisms essential for respiratory rhythmicity during normal breathing. Previously, we showed that, systemic administration of a GABA reuptake blocker in MECP2 deficient mice markedly reduced the occurrence of central apnoeas. Further, we found that, during central apnoeas, post-inspiratory drive (adductor motor) to the upper airways was enhanced in amplitude and duration in Mecp2 heterozygous female mice. Since the pontine Kölliker-Fuse area (KF) drives post-inspiration, suppresses inspiration, and can reset the respiratory oscillator phase, we hypothesized that synaptic inhibition in this area is essential for respiratory rhythm regularity. In this study, we found that: (i) Mecp2 heterozygous mice showed deficiency of GABA perisomatic bouton-like puncta and processes in the KF nucleus; (ii) blockade of GABA reuptake in the KF of RTT mice reduced breathing irregularity; (iii) conversely, blockade of GABAA receptors in the KF of healthy rats mimicked the RTT respiratory phenotype of recurrent central apnoeas and prolonged post-inspiratory activity. Our results show that reductions in synaptic inhibition within the KF induce rhythm irregularity whereas boosting GABA transmission reduces respiratory arrhythmia in a murine model of RTT. Our data suggest that manipulation of synaptic inhibition in KF may be a clinically important strategy for alleviating the life threatening respiratory disorders in RTT.

Analysis of Hemodynamic Changes and Bold Signals of Sickle Cell Disease Patients during Desaturation

Introduction: Using near-infrared spectroscopy (NIRS), previous studies have shown that sickle-cell disease (SCD) patients have low cerebral oxygen saturation values [1]. Moreover, the hemoglobin S in sickle cell disease has impaired oxygen carrying capacity [2]. Here, we propose to investigate the effect of induced desaturation on the SCD brain. In particular, we analyzed the falling functional magnetic resonance imaging (fMRI) response during hypoxia, which results from local concentration changes in paramagnetic deoxy-hemoglobin (DHB). Moreover, we also explore the near-infrared spectroscopy (NIRS) changes in oxygenated and deoxygenated hemoglobin from the human prefrontal cortex.Methods: All patients were recruited through informed consent or assent; this study obtained approval from the IRB at Children's hospital Los Angeles. Exclusion criteria included pregnancy, previous stroke, and acute chest pain and crisis hospitalization within one month. Eight patients with SCD and 20 healthy age and ethnicity-matched controls (CTL) were studied. All patients wore oxygen masks in order to control the oxygen level during the experiment in the fMRI. During the scan, the subjects breathed 1) room air for 50 s, 2) 100% N2 for 5 breaths and 3) room air for 6 minutes. The typical length of hypoxia is 5 breaths, but for patients with irregular breathing patterns the maximum duration is 20 seconds. NIRS was used to measure the hemoglobin (OHB, DHB and THB) and a tissue oxygen index (TOI), from the human prefrontal cortex. Differences oh hemoglobin measure, between the normoxia and hypoxia states, were computed and called ΔOHB, ΔDHB and ΔTOI. During resting-state fMRI scanning, subjects were instructed to close their eyes, keep still as much as possible and not to think of anything systematically. FMRI images were acquired during 8 minutes and a total of 240 volumes were collected. Imaging data was first preprocessed with the FMRIB Software Library (FSL), using standard spatial preprocessing steps: Images were (1) slice-time corrected, (2) realigned to remove physiological motion and co-registered to the MNI template space. The percent signal change from the fMRI, % BOLD, was computed based on an average signal in the GM mask.Results: 9 SCD patients (age=23±8) and 20 CTL subjects (age=21±1) were recruited. Fig 1 presents the relationship between %BOLD versus ΔOHB and % BOLD versus ΔDHB, respectively. Due to the lower oxygen affinity of hemoglobin S [1], the decrease in % BOLD (-0.093 ± 0.034) and the ΔOHB (-1.425 ± 0.588) in SCD patients are larger than the decrease in CTL individuals (% BOLD: -0.050 ± 0.021 and ΔOHB: -0.877 ± 0.539); the increase in ΔDHB (1.661 ± 0.805) in SCD patients is also greater than in the control group (ΔDHB: 0.959 ± 0.505), as shown on Figure 2. Based on the THB signal, we can detect hyperemia for most of the subjects during desaturation. Moreover, for some of the SCD patients, the reactivity is slower even at the end of the hypoxic state. We observe a slightly lower increase of ΔTHB for SCD patients, but this was found to be insignificant. This may be the result of a combination of the CBF variability in the SCD group, and of the small sample size. In our study, a decrease of ΔTOI was observed during hypoxia in both groups. The ΔTOI amplitude of the SCD group (-0.080 ± 0.023) is higher than that of the CTL group (-0.047 ± 0.024), which may be due to the SCD brain's diminished physiological adaptive capability to a hypoxic state.Conclusion: Based on a conjoint acquisition of fMRI and NIRS, this study is the first investigation of the effect of the desaturation for SCD patients. As expected, based on these preliminary results, the SCD patients are more affected by hypoxic conditions, such as a larger changes of ΔOHB, ΔDHB, ΔTOI and % BOLD and a slower reactivity, likely due to anemia, high CBF and CBV, and decreased vessel elasticity.†=equal first author contribution

Noninvasive dissection of mouse sleep using a piezoelectric motion sensor

BackgroundChanges in autonomic control cause regular breathing during NREM sleep to fluctuate during REM. Piezoelectric cage-floor sensors have been used to successfully discriminate sleep and wake states in mice based on signal features related to respiration and other movements. This study presents a classifier for noninvasively classifying REM and NREM using a piezoelectric sensor. New methodVigilance state was scored manually in 4-s epochs for 24-h EEG/EMG recordings in 20 mice. An unsupervised classifier clustered piezoelectric signal features quantifying movement and respiration into three states: one active; and two inactive with regular and irregular breathing, respectively. These states were hypothesized to correspond to Wake, NREM, and REM, respectively. States predicted by the classifier were compared against manual EEG/EMG scores to test this hypothesis. ResultsUsing only piezoelectric signal features, an unsupervised classifier distinguished Wake with high (89% sensitivity, 96% specificity) and REM with moderate (73% sensitivity, 75% specificity) accuracy, but NREM with poor sensitivity (51%) and high specificity (96%). The classifier sometimes confused light NREM sleep – characterized by irregular breathing and moderate delta EEG power – with REM. A supervised classifier improved sensitivities to 90, 81, and 67% and all specificities to over 90% for Wake, NREM, and REM, respectively. Comparison with existing methodsUnlike most actigraphic techniques, which only differentiate sleep from wake, the proposed piezoelectric method further dissects sleep based on breathing regularity into states strongly correlated with REM and NREM. ConclusionsThis approach could facilitate large-sample screening for genes influencing different sleep traits, besides drug studies or other manipulations.

Joubert Syndrome in French Canadians and Identification of Mutations in CEP104

Joubert syndrome (JBTS) is a primarily autosomal-recessive disorder characterized by a distinctive mid-hindbrain and cerebellar malformation, oculomotor apraxia, irregular breathing, developmental delay, and ataxia. JBTS is a genetically heterogeneous ciliopathy. We sought to characterize the genetic landscape associated with JBTS in the French Canadian (FC) population. We studied 43 FC JBTS subjects from 35 families by combining targeted and exome sequencing. We identified pathogenic (n = 32 families) or possibly pathogenic (n = 2 families) variants in genes previously associated with JBTS in all of these subjects, except for one. In the latter case, we found a homozygous splice-site mutation (c.735+2T>C) in CEP104. Interestingly, we identified two additional non-FC JBTS subjects with mutations in CEP104; one of these subjects harbors a maternally inherited nonsense mutation (c.496C>T [p.Arg166*]) and a de novo splice-site mutation (c.2572-2A>G), whereas the other bears a homozygous frameshift mutation (c.1328_1329insT [p.Tyr444fs*3]) in CEP104. Previous studies have shown that CEP104 moves from the mother centriole to the tip of the primary cilium during ciliogenesis. Knockdown of CEP104 in retinal pigment epithelial (RPE1) cells resulted in severe defects in ciliogenesis. These observations suggest that CEP104 acts early during cilia formation by regulating the conversion of the mother centriole into the cilia basal body. We conclude that disruption of CEP104 causes JBTS. Our study also reveals that the cause of JBTS has been elucidated in the great majority of our FC subjects (33/35 [94%] families), even though JBTS shows substantial locus and allelic heterogeneity in this population.

Hope Is Palliative

The authors reflect on the palliative value of hope when dealing with illness.

Nonrapid Eye Movement-Predominant Obstructive Sleep Apnea: Detection and Mechanism.

Obstructive sleep apnea (OSA) can be severe and present in higher numbers during rapid eye movement (REM) than nonrapid eye movement (NREM) sleep; however, OSA occurs in NREM sleep and can be predominant. In general, ventilation decreases an average 10% to 15% during transition from wakefulness to sleep, and there is variability in just how much ventilation decreases. As dynamic changes in ventilation contribute to irregular breathing and breathing during NREM sleep is mainly under chemical control, our hypothesis is that patients with a more pronounced reduction in ventilation during the transition from wakefulness to NREM sleep will have NREM- predominant rather than REM-predominant OSA. A retrospective analysis of 451 consecutive patients (apnea-hypopnea index [AHI] > 5) undergoing diagnostic polysomnography was performed, and breath-to-breath analysis of the respiratory cycle duration, tidal volume, and estimated minute ventilation before and after sleep onset were examined. Values were calculated using respiratory inductance plethysmography. The correlation between the percent change in estimated minute ventilation during wake-sleep transitions and the percentage of apnea-hypopneas in NREM sleep (%AHI in NREM; defined as (AHI-NREM) / [(AHI-NREM) + (AHI-REM)] × 100) was the primary outcome. The decrease in estimated minute ventilation during wake-sleep transitions was 15.0 ± 16.6% (mean ± standard deviation), due to a decrease in relative tidal volume. This decrease in estimated minute ventilation was significantly correlated with %AHI in NREM (r = -0.222, p < 0.01). A greater dynamic reduction in ventilation back and forth from wakefulness to sleep contributes to the NREM predominant OSA phenotype via induced ventilatory instability.

Quantitative early decision making metric for identifying irregular breathing in 4DCT.

To develop a quantitative early decision making metric for prediction of breathing pattern and irregular breathing and validate the metric in a large patient population receiving clinical phase-sorted four-dimensional computed tomography (4DCT). This study employed three patient cohorts. The first cohort contained 47 patients, imaged with a nonclinical tidal volume metric. The second cohort contained a sample of 256 patients who received a clinical 4DCT. The third cohort contained 86 patients who received three 4DCT scans at 1-week increment during the course of radiotherapy. The second and third cohorts did not have tidal volume measurements, as per standard radiation oncology clinical practice. Based on a previously published technique that used a single abdominal surrogate, the ratio of extreme inhalation tidal volume to normal inhalation tidal volume (κ) metric was calculated and the patient breathing pattern was characterized. The use of a single surrogate precluded the use of a κ determined by tidal volume, so a κ(rel) was defined based on the amplitude of the surrogate. Patients were classified as either Type 1 or Type 2, based on a previously published technique, where Type 1 patients were apneic at end of exhalation and Type 2 patients exhibited forced respiration. The Ansari-Bradley test was used to determine the statistical similarity between the Type 1 and Type 2 distributions. A Kruskal-Wallis one way analysis of variance was used to determine the statistical similarities among the classified breathing types, κ(rel), and the qualified medical physicist denoted breathing classification (regular or irregular). Receiver operator characteristic curves were used to quantitatively determine optimal cutoff value j(κ) and efficiency cutoff value (τ(κ)) κ(rel) to provide a quantitative early warning of irregular breathing during 4DCT procedures. The statistical tests show a significant consistency for the breathing pattern classifications between the physiologically measured cohort #1 and the remaining cohorts. The classification types were statistically different between Type 1 and Type 2 patients over all cohorts. Values of κ(rel) in excess of 1.72 indicated a substantial presence of irregular breathing that could negatively affect the quality of a 4DCT image dataset. Values of κ(rel) in lower than 1.45 indicated minimal presence of irregular breathing. For values of κ(rel) such that j(κ) ≤ κ(rel) ≤ τ(κ), the decision to reacquire the 4DCT would be at the discretion of the physician. This accounted for only 11.9% of the patients in this study. The magnitude of κ(rel) held consistent over three weeks of treatment for 73% of the patients in cohort #3. The decision making metric based on κ was shown to be an accurate classifier of regular and irregular breathing patterns in a large patient population. Breathing type, as defined in a previous published work, was accurately classified by κ(rel) with the use of a single respiratory surrogate compared to the physiological use of multiple respiratory surrogates. This work provided a quantitative early decision making metric to quickly and accurately assess breathing patterns as well as the presence and magnitude of irregular breathing during 4DCT.

Expiratory activation of abdominal muscle is associated with improved respiratory stability and an increase in minute ventilation in REM epochs of adult rats.

Breathing is more vulnerable to apneas and irregular breathing patterns during rapid eye movement (REM) sleep in both humans and rodents. We previously reported that robust and recurrent recruitment of expiratory abdominal (ABD) muscle activity is present in rats during REM epochs despite ongoing REM-induced muscle atonia in skeletal musculature. To develop a further understanding of the characteristics of ABD recruitment during REM epochs and their relationship with breathing patterns and irregularities, we sought to compare REM epochs that displayed ABD muscle recruitment with those that did not, within the same rats. Specifically, we investigated respiratory characteristics that preceded and followed recruitment. We hypothesized that ABD muscle recruitment would be likely to occur following respiratory irregularities and would subsequently contribute to respiratory stability and the maintenance of good ventilation following recruitment. Our data demonstrate that epochs of REM sleep containing ABD recruitments (REM(ABD+)) were characterized by increased respiratory rate variability and increased presence of spontaneous brief central apneas. Within these epochs, respiratory events that displayed ABD muscle activation were preceded by periods of increased respiratory rate variability. Onset of ABD muscle activity increased tidal volume, amplitude of diaphragmatic contractions, and minute ventilation compared with the periods preceding ABD muscle activation. These results show that expiratory muscle activity is more likely recruited when respiration is irregular and its recruitment is subsequently associated with an increase in minute ventilation and a more regular respiratory rhythm.

Superfluidity and Chaos in low dimensional circuits.

The hallmark of superfluidity is the appearance of “vortex states” carrying a quantized metastable circulating current. Considering a unidirectional flow of particles in a ring, at first it appears that any amount of scattering will randomize the velocity, as in the Drude model, and eventually the ergodic steady state will be characterized by a vanishingly small fluctuating current. However, Landau and followers have shown that this is not always the case. If elementary excitations (e.g. phonons) have higher velocity than that of the flow, simple kinematic considerations imply metastability of the vortex state: the energy of the motion cannot dissipate into phonons. On the other hand if this Landau criterion is violated the circulating current can decay. Below we show that the standard Landau and Bogoliubov superfluidity criteria fail in low-dimensional circuits. Proper determination of the superfluidity regime-diagram must account for the crucial role of chaos, an ingredient missing from the conventional stability analysis. Accordingly, we find novel types of superfluidity, associated with irregular or chaotic or breathing vortex states.

T2-weighted four dimensional magnetic resonance imaging with result-driven phase sorting.

T2-weighted MRI provides excellent tumor-to-tissue contrast for target volume delineation in radiation therapy treatment planning. This study aims at developing a novel T2-weighted retrospective four dimensional magnetic resonance imaging (4D-MRI) phase sorting technique for imaging organ/tumor respiratory motion. A 2D fast T2-weighted half-Fourier acquisition single-shot turbo spin-echo MR sequence was used for image acquisition of 4D-MRI, with a frame rate of 2-3 frames/s. Respiratory motion was measured using an external breathing monitoring device. A phase sorting method was developed to sort the images by their corresponding respiratory phases. Besides, a result-driven strategy was applied to effectively utilize redundant images in the case when multiple images were allocated to a bin. This strategy, selecting the image with minimal amplitude error, will generate the most representative 4D-MRI. Since we are using a different image acquisition mode for 4D imaging (the sequential image acquisition scheme) with the conventionally used cine or helical image acquisition scheme, the 4D dataset sufficient condition was not obviously and directly predictable. An important challenge of the proposed technique was to determine the number of repeated scans (NR) required to obtain sufficient phase information at each slice position. To tackle this challenge, the authors first conducted computer simulations using real-time position management respiratory signals of the 29 cancer patients under an IRB-approved retrospective study to derive the relationships between NR and the following factors: number of slices (NS), number of 4D-MRI respiratory bins (NB), and starting phase at image acquisition (P0). To validate the authors' technique, 4D-MRI acquisition and reconstruction were simulated on a 4D digital extended cardiac-torso (XCAT) human phantom using simulation derived parameters. Twelve healthy volunteers were involved in an IRB-approved study to investigate the feasibility of this technique. 4D data acquisition completeness (Cp) increases as NR increases in an inverse-exponential fashion (Cp = 100 - 99 × exp(-0.18 × NR), when NB = 6, fitted using 29 patients' data). The NR required for 4D-MRI reconstruction (defined as achieving 95% completeness, Cp = 95%, NR = NR,95) is proportional to NB (NR,95 ∼ 2.86 × NB, r = 1.0), but independent of NS and P0. Simulated XCAT 4D-MRI showed a clear pattern of respiratory motion. Tumor motion trajectories measured on 4D-MRI were comparable to the average input signal, with a mean relative amplitude error of 2.7% ± 2.9%. Reconstructed 4D-MRI for healthy volunteers illustrated clear respiratory motion on three orthogonal planes, with minimal image artifacts. The artifacts were presumably caused by breathing irregularity and incompleteness of data acquisition (95% acquired only). The mean relative amplitude error between critical structure trajectory and average breathing curve for 12 healthy volunteers is 2.5 ± 0.3 mm in superior-inferior direction. A novel T2-weighted retrospective phase sorting 4D-MRI technique has been developed and successfully applied on digital phantom and healthy volunteers.

Four dimensional magnetic resonance imaging optimization and implementation for magnetic resonance imaging simulation

PurposePrecise radiation therapy for abdominal lesions is complicated by respiratory motion and suboptimal soft tissue contrast from 4-dimensional (4D) computed tomography, whereas 4D magnetic resonance imaging MRI (4DMRI) provides superior tissue discrimination. This work evaluates a novel 4DMRI algorithm for motion management in radiation therapy. Methods and materialsRespiratory-triggered, T2-weighted, single-shot 4DMRI was evaluated for an open 1.0T magnetic resonance simulation platform. An in-house programmable platform was devised that translated objects for a variety of breathing patterns. Coronal 4DMRIs were acquired to evaluate the impact of number of phases on excursion and scan time. The impact of breathing period and regularity on scan time was assessed. A novel clinical 4D prototype phantom was scanned to characterize excursion and absolute volume differences between phase acquisitions. Optimized parameters were applied to abdominal 4DMRIs of 5 volunteers and 2 abdominal cancer patients on an institutional review board–approved protocol. Duty cycle, scan time, and waveform analysis were evaluated. Maximum intensity projection datasets were analyzed. ResultsTwo- to 5-fold acquisition time increase was measured for 10-phase versus 2-phase phantom experiments. Regular breathing patterns yielded higher duty cycles than irregular (48.5% and 35.9%, respectively, P < .001), whereas faster breathing rates yielded shorter 4DMRI acquisition times. Volumes of a hypodense target were underestimated 4% to 5% for 2 and 4 phases compared with 10 phases. Better agreement was obtained for 6- and 8-phase acquisitions (~3% different from 10 phase). Internal target volume centroids on minimum and maximum images across all phases were <2 mm different across all 10 phases, although slight target excursion variations (up to 4 mm) were observed. In humans, a strong negative association between breathing rate and acquisition time (Pearson’s r = −0.68, P < .05) was observed. Eight-phase acquisition times ranged from 7 to 15 minutes, depending on the patient. Conclusion4DMRI has been optimized and implemented. Irregular breathing patterns and slow breathing rate adversely impacted 4DMRI efficiency; thus, interventions such as biofeedback may be desirable.

A Randomized Controlled Trial on the Effect of Earmuffs on Intermittent Hypoxia and Bradycardia in Preterm Infants

Irregular breathing causing hypoxia and bradycardia is a common problem of preterm infants but its pathophysiology is incompletely understood. Agitation provoked by environmental noise may play a role. We wanted to know if earmuffs can at least halve the rate of intermittent hypoxia in premies. In this randomized controlled trial 31 infants (14 male; median [min.-max.] birth weight and gestational age: 1 323 g [560-1 990] and 30(1/7) weeks [25(5/7)-33(0/7)]) had the effect of earmuffs on the frequency of pulse oximeter desaturations (SpO(2) <80%) and bradycardia events (<80 beats per minute) tested, documented via a standard home monitor. Infants were measured 2 h each with or without earmuffs; the sequence of intervention was randomised. Measurement conditions were kept constant while a noise meter recorded sound pressure levels at a 1 Hz sampling rate. Median sound pressure level was 46.8 dB(A). In a pre-study, ear muffs yielded a sound reduction by 7.2 dB. 19 infants had a total of 474 desaturations. The median (25.-75. percentile) number of desaturations was 1 (1-10.5) without, and 1 (1-10) with earmuffs. The amount of infants with at least one desaturation was equal in both treatment protocols. Only 7 bradycardias occurred. The earmuffs had, in a rather quiet environment, no effect on intermittent hypoxia in these infants.

SU‐E‐J‐155: Automatic Quantitative Decision Making Metric for 4DCT Image Quality

Purpose:To develop a quantitative decision making metric for automatically detecting irregular breathing using a large patient population that received phase‐sorted 4DCT.Methods:This study employed two patient cohorts. Cohort#1 contained 256 patients who received a phasesorted 4DCT. Cohort#2 contained 86 patients who received three weekly phase‐sorted 4DCT scans. A previously published technique used a single abdominal surrogate to calculate the ratio of extreme inhalation tidal volume to normal inhalation tidal volume, referred to as the κ metric. Since a single surrogate is standard for phase‐sorted 4DCT in radiation oncology clinical practice, tidal volume was not quantified. Without tidal volume, the absolute κ metric could not be determined, so a relative κ (κrel) metric was defined based on the measured surrogate amplitude instead of tidal volume. Receiver operator characteristic (ROC) curves were used to quantitatively determine the optimal cutoff value (jk) and efficiency cutoff value (τk) of κrel to automatically identify irregular breathing that would reduce the image quality of phase‐sorted 4DCT. Discriminatory accuracy (area under the ROC curve) of κrel was calculated by a trapezoidal numeric integration technique.Results:The discriminatory accuracy of ?rel was found to be 0.746. The key values of jk and tk were calculated to be 1.45 and 1.72 respectively. For values of ?rel such that jk≤κrel≤τk, the decision to reacquire the 4DCT would be at the discretion of the physician. This accounted for only 11.9% of the patients in this study. The magnitude of κrel held consistent over 3 weeks for 73% of the patients in cohort#3.Conclusion:The decision making metric, ?rel, was shown to be an accurate classifier of irregular breathing patients in a large patient population. This work provided an automatic quantitative decision making metric to quickly and accurately assess the extent to which irregular breathing is occurring during phase‐sorted 4DCT.

WE-D-303-02: Applications of Volumetric Images Generated with a Respiratory Motion Model Based On An External Surrogate Signal

Purpose: Respiratory motion can vary significantly over the course of simulation and treatment. Our goal is to use volumetric images generated with a respiratory motion model to improve the definition of the internal target volume (ITV) and the estimate of delivered dose. Methods: Ten irregular patient breathing patterns spanning 35 seconds each were incorporated into a digital phantom. Ten images over the first five seconds of breathing were used to emulate a 4DCT scan, build the ITV, and generate a patient-specific respiratory motion model which correlated the measured trajectories of markers placed on the patients’ chests with the motion of the internal anatomy. This model was used to generate volumetric images over the subsequent thirty seconds of breathing. The increase in the ITV taking into account the full 35 seconds of breathing was assessed with ground-truth and model-generated images. For one patient, a treatment plan based on the initial ITV was created and the delivered dose was estimated using images from the first five seconds as well as ground-truth and model-generated images from the next 30 seconds. Results: The increase in the ITV ranged from 0.2 cc to 6.9 cc for the ten patients based on ground-truth information. The model predicted this increase in the ITV with an average error of 0.8 cc. The delivered dose to the tumor (D95) changed significantly from 57 Gy to 41 Gy when estimated using 5 seconds and 30 seconds, respectively. The model captured this effect, giving an estimated D95 of 44 Gy. Conclusion: A respiratory motion model generating volumetric images of the internal patient anatomy could be useful in estimating the increase in the ITV due to irregular breathing during simulation and in assessing delivered dose during treatment. This project was supported, in part, through a Master Research Agreement with Varian Medical Systems, Inc. and Radiological Society of North America Research Scholar Grant #RSCH1206.

SU‐E‐J‐192: Comparative Effect of Different Respiratory Motion Management Systems

Purpose:Irregular breathing can influence the outcome of four‐dimensional computed tomography imaging for causing artifacts. Audio‐visual biofeedback systems associated with patient‐specific guiding waveform are known to reduce respiratory irregularities. In Japan, abdomen and chest motion self‐control devices (Abches), representing simpler visual coaching techniques without guiding waveform are used instead; however, no studies have compared these two systems to date. Here, we evaluate the effectiveness of respiratory coaching to reduce respiratory irregularities by comparing two respiratory management systems.Methods:We collected data from eleven healthy volunteers. Bar and wave models were used as audio‐visual biofeedback systems. Abches consisted of a respiratory indicator indicating the end of each expiration and inspiration motion. Respiratory variations were quantified as root mean squared error (RMSE) of displacement and period of breathing cycles.Results:All coaching techniques improved respiratory variation, compared to free breathing. Displacement RMSEs were 1.43 ± 0.84, 1.22 ± 1.13, 1.21 ± 0.86, and 0.98 ± 0.47 mm for free breathing, Abches, bar model, and wave model, respectively. Free breathing and wave model differed significantly (p &lt; 0.05). Period RMSEs were 0.48 ± 0.42, 0.33 ± 0.31, 0.23 ± 0.18, and 0.17 ± 0.05 s for free breathing, Abches, bar model, and wave model, respectively. Free breathing and all coaching techniques differed significantly (p &lt; 0.05). For variation in both displacement and period, wave model was superior to free breathing, bar model, and Abches. The average reduction in displacement and period RMSE compared with wave model were 27% and 47%, respectively.Conclusion:The efficacy of audio‐visual biofeedback to reduce respiratory irregularity compared with Abches. Our results showed that audio‐visual biofeedback combined with a wave model can potentially provide clinical benefits in respiratory management, although all techniques could reduce respiratory irregularities.

SU-C-210-03: Impact of Breathing Irregularities On Gated Treatments

Purpose: To evaluate the effect of breathing irregularities on target location in gated treatments using amplitude and phase gating. Methods: 111 breathing patterns acquired using RPM system were categorized based on period and amplitude STD as regular (STD period ≤ 0.5 s, STD amplitude ≤ 1.5 mm), medium (0.5 s 1 s, STD amplitude > 3 mm). One pattern representative of the average defined population was selected per category and corresponding target motion reproduced using Quasar Respiratory Motion Phantom. Phantom in motion underwent 4D-CT scan with phase reconstruction. Gated window was defined at end of exhale and DRRs reconstructed in treatment planning at 40% (beam on) and 60% phase (beam off). Target location uncertainty was assessed by comparing gated kV triggered images continuously acquired at beam on/off on a True Beam 2.0 with corresponding DRRs. Results: Average target uncertainty with amplitude gating was in [0.4 – 1.9] mm range for the different scenarios with maximum STD of 1.2 mm for the irregular pattern. Average target uncertainty with phase gating was [1.1 – 2.2] mm for regular and medium patterns, while itmore » increased to [3.6 – 9.6] mm for the irregular pattern. Live gated motion was stable with amplitude gating, while increasing with phase gating for the irregular pattern. Treatment duration range was [68 – 160] s with amplitude and [70 – 74] s with phase gating. Conclusion: Breathing irregularities were found to affect gated treatments only when using phase gating. For regular and medium patterns no significant difference was found between the two gating strategies. Amplitude gating ensured stable gated motion within the different patterns, thus reducing intra-fraction target location variability for the irregular pattern and resulting in longer treatment duration.« less

SU‐E‐P‐59: A Graphical Interface for XCAT Phantom Configuration, Generation and Processing

Purpose:To design a comprehensive open‐source, publicly available, graphical user interface (GUI) to facilitate the configuration, generation, processing and use of the 4D Extended Cardiac‐Torso (XCAT) phantom.Methods:The XCAT phantom includes over 9000 anatomical objects as well as respiratory, cardiac and tumor motion. It is widely used for research studies in medical imaging and radiotherapy. The phantom generation process involves the configuration of a text script to parameterize the geometry, motion, and composition of the whole body and objects within it, and to generate simulated PET or CT images. To avoid the need for manual editing or script writing, our MATLAB‐based GUI uses slider controls, drop‐down lists, buttons and graphical text input to parameterize and process the phantom.Results:Our GUI can be used to: a) generate parameter files; b) generate the voxelized phantom; c) combine the phantom with a lesion; d) display the phantom; e) produce average and maximum intensity images from the phantom output files; f) incorporate irregular patient breathing patterns; and f) generate DICOM files containing phantom images. The GUI provides local help information using tool‐tip strings on the currently selected phantom, minimizing the need for external documentation. The DICOM generation feature is intended to simplify the process of importing the phantom images into radiotherapy treatment planning systems or other clinical software.Conclusion:The GUI simplifies and automates the use of the XCAT phantom for imaging‐based research projects in medical imaging or radiotherapy. This has the potential to accelerate research conducted with the XCAT phantom, or to ease the learning curve for new users. This tool does not include the XCAT phantom software itself.We would like to acknowledge funding from MRA, Varian Medical Systems Inc.