Irregular Breathing Research Articles

Dysfunctional breathing: a review of the literature and proposal for classification

Dysfunctional breathing is a term describing breathing disorders where chronic changes in breathing pattern result in dyspnoea and other symptoms in the absence or in excess of the magnitude of physiological respiratory or cardiac disease. We reviewed the literature and propose a classification system for the common dysfunctional breathing patterns described. The literature was searched using the terms: dysfunctional breathing, hyperventilation, Nijmegen questionnaire and thoraco-abdominal asynchrony. We have summarised the presentation, assessment and treatment of dysfunctional breathing, and propose that the following system be used for classification. 1) Hyperventilation syndrome: associated with symptoms both related to respiratory alkalosis and independent of hypocapnia. 2) Periodic deep sighing: frequent sighing with an irregular breathing pattern. 3) Thoracic dominant breathing: can often manifest in somatic disease, if occurring without disease it may be considered dysfunctional and results in dyspnoea. 4) Forced abdominal expiration: these patients utilise inappropriate and excessive abdominal muscle contraction to aid expiration. 5) Thoraco-abdominal asynchrony: where there is delay between rib cage and abdominal contraction resulting in ineffective breathing mechanics.This review highlights the common abnormalities, current diagnostic methods and therapeutic implications in dysfunctional breathing. Future work should aim to further investigate the prevalence, clinical associations and treatment of these presentations.

Agent kills pain like morphine, avoids side effects

A new drug candidate, when tested in mice, can kill pain like morphine and other opioids without causing some of those drugs’ serious side effects. Along with providing powerful pain relief, opioids also are addictive, can cause constipation, and can cause irregular breathing or even halt it. Opioids hit the µ-opioid receptor on neuron surfaces. Binding that receptor triggers two cellular processes simultaneously: a G protein signaling pathway that causes analgesia and a β-arrestin pathway that leads to constipation and respiratory depression. A collaborative team has now used structure-based computational drug design to find a compound that can trigger the µ-opioid receptor’s desirable G protein signaling while avoiding its β-arrestin signaling (Nature 2016, DOI: 10.1038/nature19112). The team was led by Brian K. Kobilka of Stanford University School of Medicine, Peter Gmeiner of Friedrich Alexander University of Erlangen-Nuremberg, Bryan L. Roth of the University of North Carolina School of Medicine, and

The impact of breathing guidance and prospective gating during thoracic 4DCT imaging: an XCAT study utilizing lung cancer patient motion

Two interventions to overcome the deleterious impact irregular breathing has on thoracic-abdominal 4D computed tomography (4DCT) are (1) facilitating regular breathing using audiovisual biofeedback (AVB), and (2) prospective respiratory gating of the 4DCT scan based on the real-time respiratory motion. The purpose of this study was to compare the impact of AVB and gating on 4DCT imaging using the 4D eXtended cardiac torso (XCAT) phantom driven by patient breathing patterns.We obtained simultaneous measurements of chest and abdominal walls, thoracic diaphragm, and tumor motion from 6 lung cancer patients under two breathing conditions: (1) AVB, and (2) free breathing. The XCAT phantom was used to simulate 4DCT acquisitions in cine and respiratory gated modes. 4DCT image quality was quantified by artefact detection (NCCdiff), mean square error (MSE), and Dice similarity coefficient of lung and tumor volumes (DSClung, DSCtumor). 4DCT acquisition times and imaging dose were recorded.In cine mode, AVB improved NCCdiff, MSE, DSClung, and DSCtumor by 20% (p = 0.008), 23% (p < 0.001), 0.5% (p < 0.001), and 4.0% (p < 0.003), respectively. In respiratory gated mode, AVB improved NCCdiff, MSE, and DSClung by 29% (p < 0.001), 34% (p < 0.001), 0.4% (p < 0.001), respectively. AVB increased the cine acquisitions by 15 s and reduced respiratory gated acquisitions by 31 s. AVB increased imaging dose in cine mode by 10%.This was the first study to quantify the impact of breathing guidance and respiratory gating on 4DCT imaging. With the exception of DSCtumor in respiratory gated mode, AVB significantly improved 4DCT image analysis metrics in both cine and respiratory gated modes over free breathing. The results demonstrate that AVB and respiratory-gating can be beneficial interventions to improve 4DCT for cancer radiation therapy, with the biggest gains achieved when these interventions are used simultaneously.

Expression of emotions and physiological changes during teaching

We investigated the expression of emotions while teaching in relation to a teacher’s physiological changes. We used polyvagal theory (PVT) to frame the study of teaching in a teacher education program. Donna, a teacher-researcher, experienced high levels of stress and anxiety prior to beginning to teach and throughout the lesson we used her expressed emotions as a focus for this research. We adopted event-oriented inquiry in a study of heart rate, oxygenation of the blood, and expressed emotions. Five events were identified for multilevel analysis in which we used narrative, prosodic analysis, and hermeneutic-phenomenological methods to learn more about the expression of emotions when Donna had: high heart rate (before and while teaching); low blood oxygenation (before and while teaching); and high blood oxygenation (while teaching). What we learned was consistent with the body’s monitoring system recognizing social harm and switching to the control of the unmyelinated vagus nerve, thereby shutting down organs and muscles associated with social communication—leading to irregularities in prosody and expression of emotion. In events involving high heart rate and low blood oxygenation the physiological environment was associated with less effective and sometimes confusing patterns in prosody, including intonation, pace of speaking, and pausing. In a low blood oxygenation environment there was evidence of rapid speech and shallow, irregular breathing. In contrast, during an event in which 100 % blood oxygenation occurred, prosody was perceived to be conducive to engagement and teacher expressed positive emotions, such as satisfaction, while teaching. Becoming aware of the purposes of the research and the results we obtained provided the teacher with tools to enact changes to her teaching practice, especially prosody of the voice. We regard it as a high priority to create tools to allow teachers and students, if and as necessary, to ameliorate excess emotions, and change heart rate, oxygenation levels, and breathing patterns.

ROHHAD syndrome and evolution of sleep disordered breathing.

BackgroundRapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare disease with a high mortality rate. Although nocturnal hypoventilation (NH) is central to ROHHAD, the evolution of sleep disordered breathing (SDB) is not well studied. The aim of the study was to assess early manifestations of SDB and their evolution in ROHHAD syndrome.MethodsRetrospective study of children with ROHHAD at two Canadian centers. All children with suspected ROHHAD at presentation underwent polysomnography (PSG) to screen for nocturnal hypoventilation. PSG findings at baseline and follow-up were collected. Interventions and diagnostic test results were recorded.ResultsSix children were included. The median age of rapid onset obesity and nocturnal hypoventilation (NH) was 3.5 and 7.2 years respectively. On initial screening for ROHHAD 4/6 (66.7 %) children had obstructive sleep apnea (OSA), 1/6 (16.7 %) had NH and 1/6 (16.7 %) had both OSA and NH. Follow up PSGs were performed in 5/6 children as one child died following a cardiorespiratory arrest. All children at follow up had NH and required non-invasive positive pressure ventilation. Additionally, 3/6 (50 %) children demonstrated irregular breathing patterns during wakefulness.ConclusionsChildren with ROHHAD may initially present with OSA and only develop NH later as well as dysregulation of breathing during wakefulness. The recognition of the spectrum of respiratory abnormalities at presentation and over time may be important in raising the index of suspicion of ROHHAD. Early recognition and targeted therapeutic interventions may limit morbidity and mortality associated with ROHHAD.

수면무호흡증과 단순 코골이 환자의 증상과 질환 인식도 비교

목 적 : 폐쇄성 수면무호흡증 (obstructive sleep apnea, OSA)은 비록 그 진단율이 낮지만 개인의 건강에 미칠 수 있는 위험은 상당하다. 그러나 OSA 환자가 실제 증상을 느끼는 정도는 예상보다 적으며, 질병의 심한 정도와 상관이 없는 경우가 많다. 이 연구는 OSA군과 단순코골이군 사이의 OSA 증상 인식 정도를 비교하기 위해 시행되었다. 방 법 : 임상적으로 OSA가 의심되는 282명의 피험자들이 연구에 포함되었다. 모든 피험자들은 수면다원검사를 받았고, 무호흡저호흡지수(apnea-hypopnea index, AHI)에 따라 5 이상이면 OSA군, 5 미만인 경우는 단순코골이군으로 분류되었다. 모든 피험자와 그 배우자(또는 같이 자는 사람)에 대하여 수면 장애와 질병의 인식도에 대한 설문조사를 수행하였다. 결 과 : OSA군에 비해서 단순코골이군이 코골이, 불규칙적 호흡, 무호흡 등의 수면 장애 증상을 더 잘 인식하였다. 또한 배우자(또는 같이 자는 사람)의 경우도 단순코골이군에서 피험자의 증상을 더욱 잘 인지하였다. 그렇지만 증상을 느낀 기간은 OSA군에서 유의하게 더 길었다. 상관분석에서 OSA의 증상 인식 정도는 나이, AHI, BMI, ESS 점수와 음의 상관관계를 보였다. 수면 설문과 수면다원검사 결과 중에서 오직 피츠버그수면질평가척도(Pittsburgh Sleep Quality Index)만이 OSA의 증상 인식도와 양의 상관관계를 보였다. 또한 치료 방법에 있어서 양압기, 구강내 장치에 대해 알고 있는 피험자의 비율과 선호도가 낮게 나타났다. 결 론 : 본 연구 결과에서 단순코골이 환자가 OSA 환자보다 수면 장애를 더 잘 인식하였다. AHI가 높을수록 오히려 환자의 증상에 대한 인식은 낮아졌다. Background and Objectives: Obstructive sleep apnea (OSA) is often undiagnosed but is an important risk factor affecting the health of an individual. The level of awareness of the illness among patients with OSA is low and is not correlated with severity of the illness. This study was conducted to compare awareness of OSA symptoms and illness between patients with OSA and simple snorers. Materials and Methods: Two hundred eighty-two patients who were suspected of having OSA participated in this study. All subjects underwent overnight polysomnography. Those with an apnea-hypopnea index (AHI) <TEX>${\geq}5$</TEX> were classified as the OSA group, while those with an AHI < 5 were classified as the simple snoring group. A sleep questionnaire, which included items on awareness of the illness, OSA, and sleep symptoms, was administered to all subjects and their bed-partners. Results: Simple snorers were much more aware of their symptoms such as snoring, irregular breathing, and apnea than were patients with OSA. Bed-partners of simple snorers were also more aware of the participants' sleep symptoms than were partners of patients with OSA. However, the duration of OSA symptoms was longer in the OSA group. In the correlation analysis, the level of awareness of OSA symptoms was negatively correlated with AHI, age, body mass index, and Epworth Sleepiness Scale score. Among the sleep questionnaire and polysomnography results, only Pittsburgh Sleep Quality Index was positively correlated with level of awareness of OSA symptoms. The minority of the respondents had heard about the treatment methods of continuous positive airway pressure and oral appliance and preferred them as treatment options. Conclusion: This study suggests that simple snorers are more aware of their symptoms than are patients with OSA. A higher severity of OSA, represented by a higher AHI, is correlated with lower awareness of one's OSA symptoms.

SU‐D‐202‐05: Evaluation of Four‐Dimensional Dose Reconstruction Under Breathing Irregularity

Purpose:A method of four dimensional dose reconstruction (4D‐DR) using a cine mode of an EPID to determine the delivered 4D dose distribution has been suggested. This method, however, has not been tested under irregular breathing. This study investigated their effects on 4D‐DR.Methods:The 4D‐DR attempts to find the patient's breathing phase associated with each EPID image by comparing it to pre‐generated‐EPID‐quality DRRs of every breathing phases. A lung phantom with a tumor object (3cm diameter cylinder) on a moving platform was used for this test under conditions of amplitude reduction by 1/2 during (1) the entire delivery and (2) the duration when MLC blocked the tumor (hindering the phase determination). The dose delivered to the phantom was inversely reconstructed in the associated phase image of the phantom from each EPID image based on our documented inverse method of the 4D‐DR; the phase‐specific dose was integrated, generating the 4D reconstructed dose. Forward 4D Monte Carlo calculations were used as the 4D dose of a ground truth.Results:The reconstructed dose showed 98.1% gamma pass rate for 3%/3mm under regular breathing (i.e. no amplitude reduction) when compared with the forward 4D dose. When the irregular condition (#1) was adopted for treatment, the pass rate became 94.2%. The irregularity under the MLC block (#2) showed the pass rate of 91.3%. The two conditions did not affect the reconstruction noticeably in DVH plots of the tumor and lung‐tumor.Conclusion:As long as the extent of on‐treatment motion is smaller than that of the planning CT, the 4D‐DR can be done accurately. Otherwise, ontreatment 4D CT images are necessary.

SU‐G‐BRA‐04: Simulation of Errors in Maximal Intensity Projection (MIP)‐Based Lung Tumor Internal Target Volumes (ITV) Using Real‐Time 2D MRI and Deformable Image Registration Based Lung Tumor Tracking

Purpose:To evaluate the effect of inter‐ and intra‐fractional tumor motion on the error in four‐dimensional computed tomography (4DCT) maximal intensity projection (MIP)–based lung tumor internal target volumes (ITV), using deformable image registration of real‐time 2D‐sagital cine‐mode MRI acquired during lung SBRT treatments.Methods:Five lung tumor patients underwent free breathing SBRT treatment on the ViewRay, with dose prescribed to PTV (4DCT MIP‐based ITV+3–6mm margin). Sagittal slice cine‐MR images (3.5×3.5mm pixels) were acquired through the center of the tumor at 4 frames per second throughout the treatments (3–4 fractions of 21–32 minutes duration). Tumor GTVs were contoured on the first frame of the cine and tracked throughout the treatment using off‐line optical‐flow based deformable registration implemented on a GPU cluster. Pseudo‐4DCT MIP‐based ITVs were generated from MIPs of the deformed GTV contours limited to short segments of image data. All possible pseudo‐4DCT MIP‐based ITV volumes were generated with 1s resolution and compared to the ITV volume of the entire treatment course. Varying pseudo‐4DCT durations from 10‐50s were analyzed.Results:Tumors were covered in their entirety by PTV in the patients analysed here. However, pseudo‐4DCT based ITV volumes were observed that were as small as 29% of the entire treatment‐ITV, depending on breathing irregularity and the duration of pseudo‐4DCT. With an increase in duration of pseudo‐4DCT from 10–50s the minimum volume acquired from 95% of all pseudo‐4DCTs increased from 62%–81% of the treatment ITV.Conclusion:A 4DCT MIP‐based ITV offers a ‘snap‐shot’ of breathing motion for the brief period of time the tumor is imaged on a specific day. Real time MRI over prolonged periods of time and over multiple treatment fractions shows that the accuracy of this snap‐shot varies according to inter‐ and intra‐fractional tumor motion. Further work is required to investigate the dosimetric effect of these results.

WE‐DE‐BRA‐11: A Study of Motion Tracking Accuracy of Robotic Radiosurgery Using a Novel CCD Camera Based End‐To‐End Test System

Purpose:A novel end‐to‐end test system using a CCD camera and a scintillator based phantom (XRV‐124, Logos Systems Int'l) capable of measuring the beam‐by‐beam delivery accuracy of Robotic Radiosurgery (CyberKnife) was developed and reported in our previous work. This work investigates its application in assessing the motion tracking (Synchrony) accuracy for CyberKnife.Methods:A QA plan with Anterior and Lateral beams (with 4 different collimator sizes) was created (Multiplan v5.3) for the XRV‐124 phantom. The phantom was placed on a motion platform (superior and inferior movement), and the plans were delivered on the CyberKnife M6 system using four motion patterns: static, Sine‐ wave, Sine with 15° phase shift, and a patient breathing pattern composed of 2cm maximum motion with 4 second breathing cycle. Under integral recording mode, the time‐averaged beam vectors (X, Y, Z) were measured by the phantom and compared with static delivery. In dynamic recording mode, the beam spots were recorded at a rate of 10 frames/second. The beam vector deviation from average position was evaluated against the various breathing patterns.Results:The average beam position of the six deliveries with no motion and three deliveries with Synchrony tracking on ideal motion (sinewave without phase shift) all agree within −0.03±0.00 mm, 0.10±0.04, and 0.04±0.03 in the X, Y, and X directions. Radiation beam width (FWHM) variations are within ±0.03 mm. Dynamic video record showed submillimeter tracking stability for both regular and irregular breathing pattern; however the tracking error up to 3.5 mm was observed when a 15 degree phase shift was introduced.Conclusion:The XRV‐124 system is able to provide 3D and 4D targeting accuracy for CyberKnife delivery with Synchrony. The experimental results showed sub‐millimeter delivery in phantom with excellent correlation in target to breathing motion. The accuracy was degraded when irregular motion and phase shift was introduced.

MO-FG-BRA-05: Dosimetric and Radiobiological Validation of Respiratory Gating in Conventional and Hypofractionated Radiotherapy of the Lung: Effect of Dose, Dose Rate, Gating Window and Breathing Pattern

Purpose: to evaluate the dosimetric and radiobiological consequences from having different gating windows, dose rates, and breathing patterns in gated VMAT lung radiotherapy. Methods: A novel 3D-printed moving phantom with central high and peripheral low tracer uptake regions was 4D FDG-PET/CT-scanned using ideal, patient-specific regular, and irregular breathing patterns. A scan of the stationary phantom was obtained as a reference. Target volumes corresponding to different uptake regions were delineated. Simultaneous integrated boost (SIB) 6 MV VMAT plans were produced for conventional and hypofractionated radiotherapy, using 30–70 and 100% cycle gating scenarios. Prescribed doses were 200 cGy with SIB to 240 cGy to high uptake volume for conventional, and 800 with SIB to 900 cGy for hypofractionated plans. Dose rates of 600 MU/min (conventional and hypofractionated) and flattening filter free 1400 MU/min (hypofractionated) were used. Ion chamber measurements were performed to verify delivered doses. Vials with A549 cells placed in locations matching ion chamber measurements were irradiated using the same plans to measure clonogenic survival. Differences in survival for the different doses, dose rates, gating windows, and breathing patterns were analyzed. Results: Ion chamber measurements agreed within 3% of the planned dose, for all locations, breathing patterns and gating windows. Cell survival depended on dose alone, and not on gating window, breathing pattern, MU rate, or delivery time. The surviving fraction varied from approximately 40% at 2Gy to 1% for 9 Gy and was within statistical uncertainty relative to that observed for the stationary phantom. Conclusions: Use of gated VMAT in PET-driven SIB radiotherapy was validated using ion chamber measurements and cell survival assays for conventional and hypofractionated radiotherapy.

MO-DE-207A-12: Toward Patient-Specific 4DCT Reconstruction Using Adaptive Velocity Binning

Purpose: While 4DCT provides organ/tumor motion information, it often samples data over 10–20 breathing cycles. For patients presenting with compromised pulmonary function, breathing patterns can change over the acquisition time, potentially leading to tumor delineation discrepancies. This work introduces a novel adaptive velocity-modulated binning (AVB) 4DCT algorithm that modulates the reconstruction based on the respiratory waveform, yielding a patient-specific 4DCT solution. Methods: AVB was implemented in a research reconstruction configuration. After filtering the respiratory waveform, the algorithm examines neighboring data to a phase reconstruction point and the temporal gate is widened until the difference between the reconstruction point and waveform exceeds a threshold value—defined as percent difference between maximum/minimum waveform amplitude. The algorithm only impacts reconstruction if the gate width exceeds a set minimum temporal width required for accurate reconstruction. A sensitivity experiment of threshold values (0.5, 1, 5, 10, and 12%) was conducted to examine the interplay between threshold, signal to noise ratio (SNR), and image sharpness for phantom and several patient 4DCT cases using ten-phase reconstructions. Individual phase reconstructions were examined. Subtraction images and regions of interest were compared to quantify changes in SNR. Results: AVB increased signal in reconstructed 4DCT slices for respiratory waveforms that met the prescribed criteria. For the end-exhale phases, where the respiratory velocity is low, patient data revealed a threshold of 0.5% demonstrated increased SNR in the AVB reconstructions. For intermediate breathing phases, threshold values were required to be >10% to notice appreciable changes in CT intensity with AVB. AVB reconstructions exhibited appreciably higher SNR and reduced noise in regions of interest that were photon deprived such as the liver. Conclusion: We demonstrated that patient-specific velocity-based 4DCT reconstruction is feasible. Image noise was reduced with AVB, suggesting potential applications for low-dose acquisitions and to improve 4DCT reconstruction for irregular breathing patients. The submitting institution holds research agreements with Philips Healthcare.

Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants.

This is the first clinical practice guideline from the American Academy of Pediatrics that specifically applies to patients who have experienced an apparent life-threatening event (ALTE). This clinical practice guideline has 3 objectives. First, it recommends the replacement of the term ALTE with a new term, brief resolved unexplained event (BRUE). Second, it provides an approach to patient evaluation that is based on the risk that the infant will have a repeat event or has a serious underlying disorder. Finally, it provides management recommendations, or key action statements, for lower-risk infants. The term BRUE is defined as an event occurring in an infant younger than 1 year when the observer reports a sudden, brief, and now resolved episode of ≥1 of the following: (1) cyanosis or pallor; (2) absent, decreased, or irregular breathing; (3) marked change in tone (hyper- or hypotonia); and (4) altered level of responsiveness. A BRUE is diagnosed only when there is no explanation for a qualifying event after conducting an appropriate history and physical examination. By using this definition and framework, infants younger than 1 year who present with a BRUE are categorized either as (1) a lower-risk patient on the basis of history and physical examination for whom evidence-based recommendations for evaluation and management are offered or (2) a higher-risk patient whose history and physical examination suggest the need for further investigation and treatment but for whom recommendations are not offered. This clinical practice guideline is intended to foster a patient- and family-centered approach to care, reduce unnecessary and costly medical interventions, improve patient outcomes, support implementation, and provide direction for future research. Each key action statement indicates a level of evidence, the benefit-harm relationship, and the strength of recommendation.

Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants: Executive Summary.

* Abbreviations: ALTE — : apparent life-threatening event BRUE — : brief resolved unexplained event SIDS — : sudden infant death syndrome This clinical practice guideline has 2 primary objectives. First, it recommends the replacement of the term “apparent life-threatening event” (ALTE) with a new term, “brief resolved unexplained event” (BRUE). Second, it provides an approach to evaluation and management that is based on the risk that the infant will have a repeat event or has a serious underlying disorder. Clinicians should use the term BRUE to describe an event occurring in an infant younger than 1 year when the observer reports a sudden, brief, and now resolved episode of ≥1 of the following: (1) cyanosis or pallor; (2) absent, decreased, or irregular breathing; (3) marked change in tone (hyper- or hypotonia); and (4) altered level of responsiveness. Moreover, clinicians should diagnose a BRUE only when there is no explanation for a qualifying event after conducting an appropriate history and physical examination (see Tables 2 and 3 in www.pediatrics.org/cgi/doi/10.1542/peds.2016-0590). Among infants who present for medical attention after a BRUE, the guideline identifies (1) lower-risk patients on the basis of history and physical examination, for whom evidence-based guidelines for evaluation and management are offered, and (2) higher-risk patients, whose history and physical examination suggest the need for further investigation, monitoring, and/or treatment, but for whom recommendations are not offered (because of insufficient evidence or the availability of guidance from other clinical practice guidelines specific to their presentation or diagnosis). Recommendations in this guideline apply only to lower-risk patients, who …

Impact of incorporating visual biofeedback in 4D MRI.

Precise radiation therapy (RT) for abdominal lesions is complicated by respiratory motion and suboptimal soft tissue contrast in 4D CT. 4D MRI offers improved contrast although long scan times and irregular breathing patterns can be limiting. To address this, visual biofeedback (VBF) was introduced into 4D MRI. Ten volunteers were consented to an IRB‐approved protocol. Prospective respiratory‐triggered, T2‐weighted, coronal 4D MRIs were acquired on an open 1.0T MR‐SIM. VBF was integrated using an MR‐compatible interactive breath‐hold control system. Subjects visually monitored their breathing patterns to stay within predetermined tolerances. 4D MRIs were acquired with and without VBF for 2‐ and 8‐phase acquisitions. Normalized respiratory waveforms were evaluated for scan time, duty cycle (programmed/acquisition time), breathing period, and breathing regularity (end‐inhale coefficient of variation, EI‐COV). Three reviewers performed image quality assessment to compare artifacts with and without VBF. Respiration‐induced liver motion was calculated via centroid difference analysis of end‐exhale (EE) and EI liver contours. Incorporating VBF reduced 2‐phase acquisition time (4.7±1.0 and 5.4±1.5min with and without VBF, respectively) while reducing EI‐COV by 43.8%±16.6%. For 8‐phase acquisitions, VBF reduced acquisition time by 1.9±1.6min and EI‐COVs by 38.8%±25.7% despite breathing rate remaining similar (11.1±3.8 breaths/min with vs. 10.5±2.9 without). Using VBF yielded higher duty cycles than unguided free breathing (34.4%±5.8% vs. 28.1%±6.6%, respectively). Image grading showed that out of 40 paired evaluations, 20 cases had equivalent and 17 had improved image quality scores with VBF, particularly for mid‐exhale and EI. Increased liver excursion was observed with VBF, where superior–inferior, anterior–posterior, and left–right EE‐EI displacements were 14.1±5.8, 4.9±2.1, and 1.5±1.0 mm, respectively, with VBF compared to 11.9±4.5, 3.7±2.1, and 1.2±1.4 mm without. Incorporating VBF into 4D MRI substantially reduced acquisition time, breathing irregularity, and image artifacts. However, differences in excursion were observed, thus implementation will be required throughout the RT workflow.PACS number(s): 87.55.‐x, 87.61.‐c, 87.19.xj

Rapid phase-correlated rescanning irradiation improves treatment time in carbon-ion scanning beam treatment under irregular breathing

To shorten treatment time in pencil beam scanning irradiation, we developed rapid phase-controlled rescanning (rPCR), which irradiates two or more isoenergy layers in a single gating window. Here, we evaluated carbon-ion beam dose distribution with rapid and conventional PCR (cPCR).4 dimensional computed tomography (4DCT) imaging was performed on 12 subjects with lung or liver tumors. To compensate for intrafractional range variation, the field-specific target volume (FTV) was calculated using 4DCT within the gating window (T20–T80). We applied an amplitude-based gating strategy, in which the beam is on when the tumor is within the gating window defined by treatment planning. Dose distributions were calculated for layered phase-controlled rescanning under an irregular respiratory pattern, although a single 4DCT data set was used. The number of rescannings was eight times. The prescribed doses were 48 Gy(RBE)/1 fr (where RBE is relative biological effectiveness) delivered via four beam ports to the FTV for the lung cases and 45 Gy(RBE)/2 fr delivered via two beam ports to the FTV for the liver cases.In the liver cases, the accumulated dose distributions showed an increased magnitude of hot/cold spots with rPCR compared with cPCR. The results of the dose assessment metrics for the cPCR and rPCR were very similar. The D95, Dmax, and Dmin values (cPCR/rPCR) averaged over all the patients were 96.3 ± 0.9%/96.0 ± 1.2%, 107.3 ± 3.6%/107.1 ± 2.9%, and 88.8 ± 3.2%/88.1 ± 3.1%, respectively. The treatment times in cPCR and rPCR were 110.7 s and 53.5 s, respectively.rPCR preserved dose conformation under irregular respiratory motion and reduced the total treatment time compared with cPCR.

Dysfunction of Astrocytes in the Nucleus Tractus Solitarii Leads to Cardiorespiratory Compromise

We have previously shown that saporin (SAP) microinjected into the nucleus tractus solitarii (NTS) causes loss of astrocytes while producing no immunohistochemical evidence of damage to NTS neurons. Loss of NTS astrocytes leads to loss of cardiovascular reflex control and, in some animals, sudden death as a result of asystole. Knowing that respiratory dysfunction and apnea may lead to asystole, we hypothesized that astrocytic dysfunction compromises respiratory control and may lead to apnea and sudden death. We sought to test that hypothesis in rats treated with bilateral NTS injections of the ribosomal toxin SAP, a chronic model of astrocytic loss, or fluorocitrate, which produces an acute model of astrocytic dysfunction. We first sought to determine if the loss of astrocytes due to SAP was due to necrosis or apoptosis by injection of SAP unilaterally into the NTS. We found loss of immunoreactivity for glial fibrillary acidic protein (GFAP), a marker of astrocytes, two hours, six hours, one day and seven days after SAP injection and increased immunoreactivity for the necrosis marker, receptor interacting protein (RIP), 6 hours and one day after SAP injection. In contrast, SAP treatment did not lead to apoptosis as documented by absence of positive cells in TUNEL reaction in the NTS. Injection of SAP into the NTS of neonatal rats (P13) led to loss of GFAP immunoreactivity seven days later as it also does in the adult rat brain. Therefore, in brain slices from P20–23 rats that had been treated unilaterally with SAP seven days previously, we performed patch clamp recording from neurons in the NTS and found that their intrinsic electrophysiological properties were unremarkable compared to neurons on the control side. In adult animals we monitored breathing chronically in a plethysmographic chamber after bilateral NTS microinjection of SAP. Seven days after injection, awake, treated rats, in contrast to control rats, began to manifest slow, irregular breathing patterns during eupneic breathing. During acute studies of astrocytic dysfunction, rats were anesthetized with isoflurane and respiration was monitored by intercostal electromyographic recording concurrent with recording arterial blood pressure and heart rate. Bilateral injections of fluorocitrate were made into NTS at 15 minute intervals for 2 hours. Fluorocitrate treated rats, but not rats treated with vehicle or PBS, developed slowed breathing followed by periodic apnea. These studies suggest that SAP causes necrosis of astrocytes and spares neuronal function. Either astrocytic necrosis or transient astrocytic dysfunction in the NTS interferes with normal cardiorespiratory regulation and leads to hypopnea and apnea that may contribute to death.Support or Funding InformationNIH R01HL088090 and VA Merit Review

A case of behavioural hyperventilation associated with severe central sleep apnoea and follow-up management

YL (Junior Doctor): A 36-year-old man was observed by his wife to have irregular breathing with sighs followed by recurrent episodes of prolonged breathing cessation while falling asleep. The longest...

Characterization of optical-surface-imaging-based spirometry for respiratory surrogating in radiotherapy.

To provide a comprehensive characterization of a novel respiratory surrogate that uses optical surface imaging (OSI) for accurate tidal volume (TV) measurement, dynamic airflow (TV') calculation, and quantitative breathing pattern (BP) estimation during free breathing (FB), belly breathing (BB), chest breathing (CB), and breath hold (BH). Optical surface imaging, which captures all respiration-induced torso surface motion, was applied to measure respiratory TV, TV', and BP in three common breathing patterns. Eleven healthy volunteers participated in breathing experiments with concurrent OSI-based and conventional spirometric measurements under an institutional review board approved protocol. This OSI-based technique measures dynamic TV from torso volume change (ΔVtorso = TV) in reference to full exhalation and airflow (TV' = dTV/dt). Volume conservation, excluding exchanging air, was applied for OSI-based measurements under negligible pleural pressure variation in FB, BB, and CB. To demonstrate volume conservation, a constant TV was measured during BH while the chest and belly are moving ("pretended" respiration). To assess the accuracy of OSI-based spirometry, a conventional spirometer was used as the standard for both TV and TV'. Using OSI, BP was measured as BP(OSI) = ΔVchest/ΔVtorso and BP can be visualized using BP(SHI) = SHIchest/(SHIchest + SHIbelly), where surface height index (SHI) is defined as the mean vertical distance within a region of interest on the torso surface. A software tool was developed for OSI image processing, volume calculation, and BP visualization, and another tool was implemented for data acquisition using a Bernoulli-type spirometer. The accuracy of the OSI-based spirometry is -21 ± 33 cm(3) or -3.5% ± 6.3% averaged from 11 volunteers with 76 ± 28 breathing cycles on average in FB. Breathing variations between two separate acquisitions with approximate 30-min intervals are substantial: -1% ± 34% (ranging from -64% to 40%) in TV, 4% ± 20% (ranging from -50% to 26%) in breathing period (T), and -1% ± 34% (ranging from -49% to 44%) in BP. The airflow accuracy and variation (between two exercises) are -1 ± 54 cm(3)/s and -5% ± 30%, respectively. The slope of linear regression between OSI-TV and spirometric TV is 0.93 (R(2) = 0.95) for FB, 0.96 (R(2) = 0.98) for BB, and 0.95 (R(2) = 0.95) for CB. The correlation between the two spirometric measurements is 0.98 ± 0.01. BP increases from BB, FB to CB, while TV increases from FB, BB, to CB. Under BH, 4% volume variation (range) on average was observed. The OSI-based technique provides an accurate measurement of tidal volume, airflow rate, and breathing pattern; all affect internal organ motion. This technique can be applied to various breathing patterns, including FB, BB, and CB. Substantial breathing irregularities and irreproducibility were observed and quantified with the OSI-based technique. These breathing parameters are useful to quantify breathing conditions, which could be used for effective tumor motion predictions.

Cognitive training modifies frequency EEG bands and neuropsychological measures in Rett syndrome

Rett syndrome (RS) is a childhood neurodevelopmental disorder characterized by a primary disturbance in neuronal development. Neurological abnormalities in RS are reflected in several behavioral and cognitive impairments such as stereotypies, loss of speech and hand skills, gait apraxia, irregular breathing with hyperventilation while awake, and frequent seizures. Cognitive training can enhance both neuropsychological and neurophysiological parameters. The aim of this study was to investigate whether behaviors and brain activity were modified by training in RS. The modifications were assessed in two phases: (a) after a short-term training (STT) session, i.e., after 30min of training and (b) after long-term training (LTT), i.e., after 5 days of training.Thirty-four girls with RS were divided into two groups: a training group (21 girls) who underwent the LTT and a control group (13 girls) that did not undergo LTT. The gaze and quantitative EEG (QEEG) data were recorded during the administration of the tasks. A gold-standard eye-tracker and a wearable EEG equipment were used. Results suggest that the participants in the STT task showed a habituation effect, decreased beta activity and increased right asymmetry. The participants in the LTT task looked faster and longer at the target, and show increased beta activity and decreased theta activity, while a leftward asymmetry was re-established. The overall result of this study indicates a positive effect of long-term cognitive training on brain and behavioral parameters in subject with RS.

Technical aspects of real time positron emission tracking for gated radiotherapy.

Respiratory motion can lead to treatment errors in the delivery of radiotherapy treatments. Respiratory gating can assist in better conforming the beam delivery to the target volume. We present a study of the technical aspects of a real time positron emission tracking system for potential use in gated radiotherapy. The tracking system, called PeTrack, uses implanted positron emission markers and position sensitive gamma ray detectors to track breathing motion in real time. PeTrack uses an expectation-maximization algorithm to track the motion of fiducial markers. A normalized least mean squares adaptive filter predicts the location of the markers a short time ahead to account for system response latency. The precision and data collection efficiency of a prototype PeTrack system were measured under conditions simulating gated radiotherapy. The lung insert of a thorax phantom was translated in the inferior-superior direction with regular sinusoidal motion and simulated patient breathing motion (maximum amplitude of motion ±10 mm, period 4 s). The system tracked the motion of a (22)Na fiducial marker (0.34 MBq) embedded in the lung insert every 0.2 s. The position of the was marker was predicted 0.2 s ahead. For sinusoidal motion, the equation used to model the motion was fitted to the data. The precision of the tracking was estimated as the standard deviation of the residuals. Software was also developed to communicate with a Linac and toggle beam delivery. In a separate experiment involving a Linac, 500 monitor units of radiation were delivered to the phantom with a 3 × 3 cm photon beam and with 6 and 10 MV accelerating potential. Radiochromic films were inserted in the phantom to measure spatial dose distribution. In this experiment, the period of motion was set to 60 s to account for beam turn-on latency. The beam was turned off when the marker moved outside of a 5-mm gating window. The precision of the tracking in the IS direction was 0.53 mm for a sinusoidally moving target, with an average count rate ∼250 cps. The average prediction error was 1.1 ± 0.6 mm when the marker moved according to irregular patient breathing motion. Across all beam deliveries during the radiochromic film measurements, the average prediction error was 0.8 ± 0.5 mm. The maximum error was 2.5 mm and the 95th percentile error was 1.5 mm. Clear improvement of the dose distribution was observed between gated and nongated deliveries. The full-width at halfmaximum of the dose profiles of gated deliveries differed by 3 mm or less than the static reference dose distribution. Monitoring of the beam on/off times showed synchronization with the location of the marker within the latency of the system. PeTrack can track the motion of internal fiducial positron emission markers with submillimeter precision. The system can be used to gate the delivery of a Linac beam based on the position of a moving fiducial marker. This highlights the potential of the system for use in respiratory-gated radiotherapy.