Optimized quantitative mapping of cardiopulmonary oscillations using hyperpolarized 129 Xe gas exchange MRI: Digital phantoms and clinical evaluation in CTEPH.

PURPOSE: The interaction between 129 Xe atoms and pulmonary capillary red blood cells provides cardiogenic signal oscillations that display sensitivity to precapillary and postcapillary pulmonary hypertension. Recently, such oscillations have been spatially mapped, but little is known about optimal reconstruction or sensitivity to artifacts. In this study, we use digital phantom simulations to specifically optimize keyhole reconstruction for oscillation imaging. We then use this optimized method to re-establish healthy reference values and quantitatively evaluate microvascular flow changes in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after pulmonary thromboendarterectomy (PTE). METHODS: A six-zone digital lung phantom was designed to investigate the effects of radial views, key radius, and SNR. One-point Dixon 129 Xe gas exchange MRI images were acquired in a healthy cohort (n = 17) to generate a reference distribution and thresholds for mapping red blood cell oscillations. These thresholds were applied to 10 CTEPH participants, with 6 rescanned following PTE. RESULTS: For undersampled acquisitions, a key radius of 0.14 k max $$ 0.14{k}_{\mathrm{max}} $$ was found to optimally resolve oscillation defects while minimizing excessive heterogeneity. CTEPH participants at baseline showed higher oscillation defect + low (32 ± 14%) compared with healthy volunteers (18 ± 12%, p < 0.001). For those scanned both before and after PTE, oscillation defect + low decreased from 37 ± 13% to 23 ± 14% (p = 0.03). CONCLUSIONS: Digital phantom simulations have informed an optimized keyhole reconstruction technique for gas exchange images acquired with standard 1-point Dixon parameters. Our proposed methodology enables more robust quantitative mapping of cardiogenic oscillations, potentially facilitating effective regional quantification of microvascular flow impairment in patients with pulmonary vascular diseases such as CTEPH.

Enhanced Recovery After Surgery (ERAS) Spine Pathways and the Role of Perioperative Checklists.

Enhanced recovery after surgery (ERAS) proposes a multimodal, evidence-based approach to perioperative care. ERAS pathways have been shown to help reduce complications, hospital length of stay (LOS), 30-day readmission rates, pain scores, and ultimately surgical costs, while improving patient satisfaction scores and outcomes in multiple surgical subspecialties [1-6]. Numerous specialties have implemented ERAS programs across the globe, providing a foundation for spine surgeons to begin the process themselves. Over the last few years, a significant number of papers have been addressing ERAS pathways for spinal surgery [7-19]. The majority have addressed the lumbar spine [9, 20-26]. The number of cervical ERAS pathways has been limited [27-29]. Many spine programs have begun the implementation of ERAS pathways, incorporating principles and interventions to various spine surgical procedures. Although differences in implementation across programs exist, there are a few common elements that promote a successful enhanced recovery approach [11, 16, 23, 25, 30-33]. All spinal ERAS pathways have three major elements, which are preoperative, perioperative, and postoperative phases. Within these phases some common elements include preoperative and intraoperative surgical checklists. Intraoperative checklist in addition to the "surgical time out" has been integrated into the workflow of most hospitals doing surgeries and have become a standard of care. The surgical checklist is designed to help reduce surgical errors and prevent wrong site/patient surgeries. Several surgical checklists have been developed throughout the years. Despite these safety protocols wrong site/level and other surgical errors continue to occur. Many cases of wrong level spine surgery (WLSS) still occur even when intraoperative imaging is performed [34, 35]. One survey reported that about 50% of spine surgeons have performed at least one WLSS during their career [36, 37]. Another survey reported that 36% of spine surgeons had performed at least one WLSS that was not recognized intraoperatively [38]. On a similar account, about 30% of spine surgery fellows have experienced wrong-site surgery [39]. From raw incidence rates, WLSS may seem rare, but these surveys show that the experience of WLSS is rather common among spine surgeons. WLSS is not yet a "never event." This may be due to poor quality of the intraoperative images, hindering subsequent level identification [34, 35, 38, 40]. Errors in interpretation of the imaging may also occur, including inconsistency in numbering vertebrae, inconsistency in landmark usage for level counting, and problems with numbering vertebrae due to lumbosacral transitional vertebrae (LSTV) and other anatomical variants [34, 38, 41-43]. This chapter will describe a framework for the development and implementation of ERAS pathway for patients undergoing spine surgery. In addition, we will propose preoperative imaging guidelines and a comprehensive spine surgical checklist to incorporate into the perioperative phase to help reduce further surgical errors and WLSS.

Contrast-Enhanced In-Phase Dixon Sequence: Impact on Biopsy Clip Detection on Breast MRI.

BACKGROUND. Identification of breast biopsy clips using conventional MRI sequences may be challenging. A contrast-enhanced in-phase Dixon sequence may have greater conspicuity for areas of susceptibility compared with standard clinical sequences. OBJECTIVE. The purpose of this article is to compare detection of breast biopsy clips on MRI between the contrast-enhanced in-phase Dixon sequence and three routine clinical sequences. METHODS. This retrospective study included 164 patients (mean age, 50.3 years) with a total of 281 breast biopsy clips who underwent contrast-enhanced breast MRI between January 2, 2019, and April 16, 2020. Three radiologists, blinded to the clip location and sequence used, independently annotated biopsy clip locations on three clinical sequences (T1-weighted non-fat-suppressed [NFS], STIR, and first phase from dynamic contrast-enhanced T1-weighted fat-suppressed [FS]) and on a contrast-enhanced in-phase Dixon sequence and then recorded confidence scores (1-4 scale). A study coordinator used all available imaging and reports to localize clips on MRI, which served as the reference standard. A physicist measured clip CNR. Sequences were compared using the McNemar test and two-tailed Wilcoxon signed rank tests. RESULTS. Among the three readers, pooled sensitivity and PPV were 78.2% and 96.2% for T1-weighted NFS, 26.6% and 92.7% for STIR, 61.7% and 95.9% for contrast-enhanced T1-weighted FS, and 85.1% and 95.1% for contrast-enhanced in-phase Dixon sequence. Pooled sensitivity was higher for contrast-enhanced in-phase Dixon sequence than for the other sequences (all p < .05); pooled PPV was not significantly different between contrast-enhanced in-phase Dixon and the other sequences (all p > .05). Mean confidence scores (pooled across readers for true-positive assessments) and mean CNR were 3.0 ± 0.9 (SD) and 1.21 ± 0.61 for T1-weighted NFS, 1.7 ± 0.9 and 0.57 ± 0.69 for STIR, 2.5 ± 1.0 and 0.54 ± 0.61 for contrast-enhanced T1-weighted FS, and 3.5 ± 0.8 and 4.05 ± 2.6 for the contrast-enhanced in-phase Dixon sequence. Pooled mean confidence scores and CNR were higher for contrast-enhanced in-phase Dixon than for the other sequences (all p < .001). CONCLUSION. Compared with clinical sequences, the contrast-enhanced in-phase Dixon sequence had higher sensitivity for detecting breast biopsy clips on MRI and higher reader confidence and CNR, without change in PPV. CLINICAL IMPACT. The contrast-enhanced in-phase Dixon sequence may help address a current challenge in clinical breast MRI interpretation.

Global transcriptional repression in C. elegans germline precursors by regulated sequestration of TAF-4.

In C. elegans, four asymmetric divisions, beginning with the zygote (P0), generate transcriptionally repressed germline blastomeres (P1-P4) and somatic sisters that become transcriptionally active. The protein PIE-1 represses transcription in the later germline blastomeres but not in the earlier germline blastomeres P0 and P1. We show here that OMA-1 and OMA-2, previously shown to regulate oocyte maturation, repress transcription in P0 and P1 by binding to and sequestering in the cytoplasm TAF-4, a component critical for assembly of TFIID and the pol II preinitiation complex. OMA-1/2 binding to TAF-4 is developmentally regulated, requiring phosphorylation by the DYRK kinase MBK-2, which is activated at meiosis II after fertilization. OMA-1/2 are normally degraded after the first mitosis, but ectopic expression of wild-type OMA-1 is sufficient to repress transcription in both somatic and later germline blastomeres. We propose that phosphorylation by MBK-2 serves as a developmental switch, converting OMA-1/2 from oocyte to embryo regulators.

Artificial intelligence and machine learning overview in pathology & laboratory medicine: A general review of data preprocessing and basic supervised concepts.

Machine learning (ML) is becoming an integral aspect of several domains in medicine. Yet, most pathologists and laboratory professionals remain unfamiliar with such tools and are unprepared for their inevitable integration. To bridge this knowledge gap, we present an overview of key elements within this emerging data science discipline. First, we will cover general, well-established concepts within ML, such as data type concepts, data preprocessing methods, and ML study design. We will describe common supervised and unsupervised learning algorithms and their associated common machine learning terms (provided within a comprehensive glossary of terms that are discussed within this review). Overall, this review will offer a broad overview of the key concepts and algorithms in machine learning, with a focus on pathology and laboratory medicine. The objective is to provide an updated useful reference for those new to this field or those who require a refresher.

Complications of Anterior Cervical Discectomy and Fusion.

Anterior cervical discectomy and fusion (ACDF) is the most common surgery performed on the cervical spine, and the number of its cases has tripled over the last two decades. Although this intervention is typically safe and effective, it carries an inherent complication risk, which should not be underestimated. Improvements in surgical techniques and advances in interbody fusion devices and plating systems have certainly reduced the rate of postoperative morbidity, but despite such progress, surgeons need to beware consistently of the potential complications, inform the patient of their possibility, and have a management strategy as they develop. This review discusses postoperative morbidity encountered in recently reported large studies on ACDF and highlights the senior author's own single-surgeon experience with 2579 such procedures performed between 1998 and 2017. In his clinical series, which is the largest one reported to date, the overall complication rate was 7.0% (180 cases), and dysphagia (1.9% of cases), graft/hardware failures (1.3% of cases), and postoperative hematomas (0.9% of cases) were noted most frequently. Understanding of the risk and clinical impact of complications after ACDF is very important and every effort should be put on their possible avoidance and on appropriate management when they do occur.

A Hybrid Stainless-Steel SPME Microneedle Electrode Sensor for Dual Electrochemical and GC-MS Analysis.

A mechanically robust in-tube stainless steel microneedle solid phase microextraction (SPME) platform for dual electrochemical and chromatographic detection has been demonstrated. The SPME microneedle was fabricated by layer-by-layer (LbL) in-tube coating, consisting of carbon nanotube (CNT)/cellulose nanocrystal (CNC) film layered with an electrically conductive polyaniline (PANI) hydrogel layer (PANI@CNT/CNC SPME microneedle (MN)). The PANI@CNT/CNC SPME MN showed effective analysis of caffeine by GC-MS with an LOD of 26 mg/L and excellent precision across the dynamic range. Additionally, the PANI@CNT/CNC SPME MN demonstrated a 67% increase in sensitivity compared to a commercial SPME fiber, while being highly robust for repeated use without loss in performance. For electrochemical detection, the PANI@CNT/CNC SPME MN showed excellent performance for the detection of 3-caffeoylquinic acid (3-CQA). The dynamic range and limits of detection (LOD) for 3-CQA analysis were 75-448 mg/L and 11 mg/L, respectively. The PANI@CNT/CNC SPME MN was demonstrated to accurately determine the caffeine content and 3-CQA in tea samples and dark roast coffee, respectively. The PANI@CNT/CNC SPME MN was used for semiquantitative antioxidant determination and composition analysis in kiwi fruit using electrochemistry and SPME-coupled GC-MS, respectively.

Person-Centered Interventions for Autistic Adolescents Ages 13-19 Years (2013-2021).

Systematic review briefs provide a summary of findings from systematic reviews developed in conjunction with the Evidence-Based Practice Program of the American Occupational Therapy Association. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings from a systematic review of family- and person-centered planning interventions for autistic1 adolescents aged 13-19 yr gathered from literature published between 2013 and 2021.

Family-Centered Interventions for Children on the Autism Spectrum (2013-2021).

Systematic review briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. The authors completed a systematic review of family- and person-centered planning interventions for families of autistic1 children, or autistic adolescents and adults gathered from literature published between 2013 and 2021. This systematic review brief presents findings from the six included articles that focused on family-centered planning interventions. Emerging evidence from these six studies supports the use of coaching interventions with caregivers of children on the autism spectrum to address both child and parent outcomes. These outcomes include individualized goals; caregiver sense of competence, empowerment, or self-efficacy; occupational performance of children and mothers; and caregiver satisfaction with their child's occupational performance.

Person-Centered Interventions for Autistic Adults Ages 18+ (2013-2021).

Systematic review briefs provide a summary of the findings from systematic reviews developed in conjunction with the Evidence-Based Practice Program of the American Occupational Therapy Association. Each systematic review brief summarizes the evidence for a theme related to a systematic review topic. This systematic review brief presents findings from a systematic review of family- and person-centered planning interventions for autistic1 adults aged 18+ years gathered from literature published between 2013 and 2021.

Molecularly Imprinted Polymer-Modified Microneedle Sensor for the Detection of Imidacloprid Pesticides in Food Samples.

A portable, molecularly imprinted polymer (MIP)-based microneedle (MN) sensor for the electrochemical detection of imidacloprid (IDP) has been demonstrated. The MN sensor was fabricated via layer-by-layer (LbL) in-tube coating using a carbon nanotube (CNT)/cellulose nanocrystal (CNC) composite, and an IDP-imprinted polyaniline layer co-polymerized with imidazole-functionalized CNCs (PANI-co-CNC-Im) as the biomimetic receptor film. The sensor, termed MIP@CNT/CNC MN, was analyzed using both cyclic voltammetry (CV) and differential pulse voltammetry (DPV) and showed excellent electrochemical performance for the detection of IDP. The CV detection range for IDP was 2.0-99 µM, with limits of detection (LOD) of 0.35 µM, while the DPV detection range was 0.20-92 µM with an LOD of 0.06 µM. Additionally, the MIP@CNT/CNC MN sensor showed excellent reusability and could be used up to nine times with a 1.4 % relative standard deviation (% RSD) between uses. Lastly, the MIP@CNT/CNC MN sensor successfully demonstrated the quantification of IDP in a honey sample.

Special Issue on Occupational Therapy With Neurodivergent People.

The neurodiversity movement presents a significant opportunity for occupational therapy practitioners to meet the needs of neurodivergent people across the life course The term neurodiverse includes autistic people and people with intellectual disabilities, attention deficit hyperactivity disorder, obsessive-compulsive disorder, and several other mental health conditions. Research shows that neurodivergent people continue to need occupational therapy beyond the end of high school, when most supports and services end for them. Despite research showing that the needs of neurodiverse populations continue throughout the life course, research also shows that services for this population seem to taper as they progress through the public school system. The studies in this issue add to the body of literature supporting the role of occupational therapy practitioners in meeting the needs of neurodiverse people for services and supports through all stages of life.

Reciprocal signaling by Wnt and Notch specifies a muscle precursor in the C. elegans embryo.

The MS blastomere produces one-third of the body wall muscles (BWMs) in the C. elegans embryo. MS-derived BWMs require two distinct cell-cell interactions, the first inhibitory and the second, two cell cycles later, required to overcome this inhibition. The inductive interaction is not required if the inhibitory signal is absent. Although the Notch receptor GLP-1 was implicated in both interactions, the molecular nature of the two signals was unknown. We now show that zygotically expressed MOM-2 (Wnt) is responsible for both interactions. Both the inhibitory and the activating interactions require precise spatiotemporal expression of zygotic MOM-2, which is dependent upon two distinct Notch signals. In a Notch mutant defective only in the inductive interaction, MS-derived BWMs can be restored by preventing zygotic MOM-2 expression, which removes the inhibitory signal. Our results suggest that the inhibitory interaction ensures the differential lineage specification of MS and its sister blastomere, whereas the inductive interaction promotes the expression of muscle-specifying genes by modulating TCF and ß-catenin levels. These results highlight the complexity of cell fate specification by cell-cell interactions in a rapidly dividing embryo.

Comparison of Molecular Subtyping and Antimicrobial Resistance Detection Methods Used in a Large Multistate Outbreak of Extensively Drug-Resistant Campylobacter jejuni Infections Linked to Pet Store Puppies.

Campylobacter jejuni is a leading cause of enteric bacterial illness in the United States. Traditional molecular subtyping methods, such as pulsed-field gel electrophoresis (PFGE) and 7-gene multilocus sequence typing (MLST), provided limited resolution to adequately identify C. jejuni outbreaks and separate out sporadic isolates during outbreak investigations. Whole-genome sequencing (WGS) has emerged as a powerful tool for C. jejuni outbreak detection. In this investigation, 45 human and 11 puppy isolates obtained during a 2016-2018 outbreak linked to pet store puppies were sequenced. Core genome multilocus sequence typing (cgMLST) and high-quality single nucleotide polymorphism (hqSNP) analysis of the sequence data separated the isolates into the same two clades containing minor within-clade differences; however, cgMLST analysis does not require selection of an appropriate reference genome, making the method preferable to hqSNP analysis for Campylobacter surveillance and cluster detection. The isolates were classified as sequence type 2109 (ST2109)-a rarely seen MLST sequence type. PFGE was performed on 38 human and 10 puppy isolates; PFGE patterns did not reliably predict clustering by cgMLST analysis. Genetic detection of antimicrobial resistance determinants predicted that all outbreak-associated isolates would be resistant to six drug classes. Traditional antimicrobial susceptibility testing (AST) confirmed a high correlation between genotypic and phenotypic antimicrobial resistance determinations. WGS analysis linked C. jejuni isolates in humans and pet store puppies even when canine exposure information was unknown, aiding the epidemiological investigation during the outbreak. WGS data were also used to quickly identify the highly drug-resistant profile of these outbreak-associated C. jejuni isolates.

Scattering of Co-Current Surface Waves on an Analogue Black Hole.

We report on what is to our knowledge the first scattering experiment of surface waves on an accelerating transcritical flow, which in the analogue gravity context is described by an effective spacetime with a black-hole horizon. This spacetime has been probed by an incident co-current wave, which partially scatters into an outgoing countercurrent wave on each side of the horizon. The measured scattering amplitudes are compatible with the predictions of the hydrodynamical theory, where the kinematical description in terms of the effective metric is exact.

An Update on the Role of Immunohistochemistry in the Evaluation of Gastrointestinal Tract Disorders.

As in other organ systems, immunohistochemistry (IHC) serves as an ancillary diagnostic tool for a wide variety of neoplastic and non-neoplastic disorders, including infections, work-up of inflammatory conditions, and subtyping neoplasms of the gastrointestinal (GI) tract. In addition, IHC is also used to detect a variety of prognostic and predictive molecular biomarkers for carcinomas of the GI tract. The purpose of this review is to highlight the use of IHC in common diagnostic scenarios throughout the tubular GI tract. The clinical indication and guidelines for performing IHC for detecting Helicobacter pylori is discussed along with role of gastrin and neuroendocrine markers in the diagnosis of autoimmune metaplastic atrophic gastritis. The major portion of this review discusses the use of IHC in the diagnostic workup of malignant neoplasms of the GI tract, such as adenocarcinoma versus squamous cell carcinoma, workup of poorly differentiated malignant neoplasms, and evaluation of uncommon gastric neoplasms (alpha-feto protein-producing carcinomas) and switch/sucrose-nonfermenting complex-deficient carcinomas. Lastly, localization of neuroendocrine tumors of unknown origin to aid clinical management, as well as HPV-driven anal neoplasia and IHC in the workup of basaloid anal neoplasms are also reviewed.

Glycemic Outcomes in Adults With Type 2 Diabetes Participating in a Continuous Glucose Monitor-Driven Virtual Diabetes Clinic: Prospective Trial.

BACKGROUND: The Onduo virtual diabetes clinic (VDC) for people with type 2 diabetes (T2D) combines a mobile app, remote personalized lifestyle coaching, connected devices, and live video consultations with board-certified endocrinologists for medication management and prescription of real-time continuous glucose monitoring (RT-CGM) devices for intermittent use. OBJECTIVE: This prospective single-arm study evaluated glycemic outcomes associated with participation in the Onduo VDC for 4 months. METHODS: Adults aged ≥18 years with T2D and a baseline glycated hemoglobin (HbA1c) of ≥8% to ≤12% were enrolled from 2 primary care centers from February 2019 to October 2019. Participants were asked to engage at ≥1 time per week with their care team and to participate in a telemedicine consultation with a clinic endocrinologist for diabetes medication review. Participants were asked to use a RT-CGM device and wear six 10-day sensors (total 60 days of sensor wear) intermittently over the course of 4 months. The primary outcome was change in HbA1c at 4 months from baseline. Other endpoints included change in weight and in RT-CGM glycemic metrics, including percent time <70, 70-180, 181-250, and >250 mg/dL. Changes in blood pressure and serum lipids at 4 months were also evaluated. RESULTS: Participants (n=55) were 57.3 (SD 11.6) years of age, body mass index 33.7 (SD 7.2), and 40% (22/55) female. HbA1c decreased significantly by 1.6% (SD 1%; P<.001). When stratified by baseline HbA1c of 8.0% to 9.0% (n=36) and >9.0% (n=19), HbA1c decreased by 1.2% (SD 0.6%; P<.001) and 2.4% (SD 1.3%; P<.001), respectively. Continuous glucose monitoring-measured (n=43) percent time in range (TIR) 70-180 mg/dL increased by 10.2% (SD 20.5%; P=.002), from 65.4% (SD 23.2%) to 75.5% (SD 22.7%), which was equivalent to a mean increase of 2.4 hours TIR per day. Percent time 181-250 mg/dL and >250 mg/dL decreased by 7.2% (SD 15.4; P=.005) and 3.0% (SD 9.4; P=.01), respectively. There was no change in percent time <70 mg/dL. Mean weight decreased by 9.0 lb (SD 10.4; P<.001). Significant improvements were also observed in systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and triglycerides (P=.04 to P=<.001). CONCLUSIONS: Participants in the Onduo VDC experienced significant improvement in HbA1c, increased TIR, decreased time in hyperglycemia, and no increase in hypoglycemia at 4 months. Improvements in other metabolic health parameters including weight and blood pressure were also observed. In conclusion, the Onduo VDC has potential to support people with T2D and their clinicians between office visits by increasing access to specialty care and advanced diabetes technology including RT-CGM. TRIAL REGISTRATION: ClinicalTrials.gov NCT03865381; https://clinicaltrials.gov/ct2/show/NCT03865381.

Mapping and correcting hyperpolarized magnetization decay with radial keyhole imaging.

PURPOSE: Hyperpolarized (HP) media enable biomedical imaging applications that cannot be achieved with conventional MRI contrast agents. Unfortunately, quantifying HP images is challenging, because relaxation and radio-frequency pulsing generate spatially varying signal decay during acquisition. We demonstrate that, by combining center-out k-space sampling with postacquisition keyhole reconstruction, voxel-by-voxel maps of regional HP magnetization decay can be generated with no additional data collection. THEORY AND METHODS: Digital phantom, HP 129 Xe phantom, and in vivo 129 Xe human (N = 4 healthy; N = 2 with cystic fibrosis) imaging was performed using radial sampling. Datasets were reconstructed using a postacquisition keyhole approach in which 2 temporally resolved images were created and used to generate maps of regional magnetization decay following a simple analytical model. RESULTS: Mean, keyhole-derived decay terms showed excellent agreement with the decay used in simulations (R2 = 0.996) and with global attenuation terms in HP 129 Xe phantom imaging (R2 > 0.97). Mean regional decay from in vivo imaging agreed well with global decay values and displayed spatial heterogeneity that matched expected variations in flip angle and oxygen partial pressure. Moreover, these maps could be used to correct variable signal decay across the image volume. CONCLUSIONS: We have demonstrated that center-out trajectories combined with keyhole reconstruction can be used to map regional HP signal decay and to quantitatively correct images. This approach may be used to improve the accuracy of quantitative measures obtained from hyperpolarized media. Although validated with gaseous HP 129 Xe in this work, this technique can be generalized to any hyperpolarized agent.

A protocol for quantifying cardiogenic oscillations in dynamic 129 Xe gas exchange spectroscopy: The effects of idiopathic pulmonary fibrosis.

The spectral parameters of hyperpolarized 129 Xe exchanging between airspaces, interstitial barrier, and red blood cells (RBCs) are sensitive to pulmonary pathophysiology. This study sought to evaluate whether the dynamics of 129 Xe spectroscopy provide additional insight, with particular focus on quantifying cardiogenic oscillations in the RBC resonance. 129 Xe spectra were dynamically acquired in eight healthy volunteers and nine subjects with idiopathic pulmonary fibrosis (IPF). 129 Xe FIDs were collected every 20 ms (TE  = 0.932 ms, 512 points, dwell time = 32 µs, flip angle ≈ 20°) during a 16 s breathing maneuver. The FIDs were pre-processed using the spectral improvement by Fourier thresholding technique (SIFT) and fit in the time domain to determine the airspace, interstitial barrier, and RBC spectral parameters. The RBC and gas resonances were fit to a Lorentzian lineshape, while the barrier was fit to a Voigt lineshape to account for its greater structural heterogeneity. For each complex resonance the amplitude, chemical shift, linewidth(s), and phase were calculated. The time-averaged spectra confirmed that the RBC to barrier amplitude ratio (RBC:barrier ratio) and RBC chemical shift are both reduced in IPF subjects. Their temporal dynamics showed that all three 129 Xe resonances are affected by the breathing maneuver. Most notably, several RBC spectral parameters exhibited prominent oscillations at the cardiac frequency, and their peak-to-peak variation differed between IPF subjects and healthy volunteers. In the IPF cohort, oscillations were more prominent in the RBC amplitude (16.8 ± 5.2 versus 9.7 ± 2.9%; P = 0.008), chemical shift (0.43 ± 0.33 versus 0.083 ± 0.05 ppm; P < 0.001), and phase (7.7 ± 5.6 versus 1.4 ± 0.8°; P < 0.001). Dynamic 129 Xe spectroscopy is a simple and sensitive tool that probes the temporal variability of gas exchange and may prove useful in discerning the underlying causes of its impairment.

Multireader Determination of Clinically Significant Obstruction Using Hyperpolarized 129Xe-Ventilation MRI.

OBJECTIVE: The objective of our study was to identify the magnitude and distribution of ventilation defect scores (VDSs) derived from hyperpolarized (HP) 129Xe-MRI associated with clinically relevant airway obstruction. MATERIALS AND METHODS: From 2012 to 2015, 76 subjects underwent HP 129Xe-MRI (48 healthy volunteers [mean age ± SD, 54 ± 17 years]; 20 patients with asthma [mean age, 44 ± 20 years]; eight patients with chronic obstructive pulmonary disease [mean age, 67 ± 5 years]). All subjects underwent spirometry 1 day before MRI to establish the presence of airway obstruction (forced expiratory volume in 1 second-to-forced vital capacity ratio [FEV1/FVC] < 70%). Five blinded readers assessed the degree of ventilation impairment and assigned a VDS (range, 0-100%). Interreader agreement was assessed using the Fleiss kappa statistic. Using FEV1/FVC as the reference standard, the optimum VDS threshold for the detection of airway obstruction was estimated using ROC curve analysis with 10-fold cross-validation. RESULTS: Compared with the VDSs in healthy subjects, VDSs in patients with airway obstruction were significantly higher (p < 0.0001) and significantly correlated with disease severity (r = 0.66, p < 0.0001). Ventilation defects in subjects with airway obstruction did not show a location-specific pattern (p = 0.158); however, defects in healthy control subjects were more prevalent in the upper lungs (p = 0.014). ROC curve analysis yielded an optimal threshold of 12.4% ± 6.1% (mean ± SD) for clinically significant VDS. Interreader agreement for 129Xe-MRI was substantial (κ = 0.71). CONCLUSION: This multireader study of a diverse cohort of patients and control subjects suggests a 129Xe-ventilation MRI VDS of 12.4% or greater represents clinically significant obstruction.