Evolution of a laboratory mechanomyograph.

Mechanomyography is currently the accepted laboratory reference standard for quantitative neuromuscular blockade monitoring. Mechanomyographs are not commercially available. Previously, a mechanomyograph was built by our laboratory and used in several clinical studies. It was subsequently redesigned to improve its usability and functionality and to accommodate a wider range of hand sizes and shapes using an iterative design process. Each version of the redesigned device was initially tested for usability and functionality in the lab with the investigators as subjects without electrical stimulation. The redesigned devices were then assessed on patients undergoing elective surgery under general anesthesia without neuromuscular blocking drugs. Since the patients were not paralyzed, the expected train-of-four ratio was 1.0. The device accuracy and precision were represented by the train-of-four ratio mean and standard deviation. If issues with the device's useability or functionality were discovered, changes were made, and the redesign processes repeated. The final mechanomyograph design was used to collect 2,362 train-of-four ratios from 21 patients. The mean and standard deviation of the train-of-four ratios were 0.99 ± 0.030. Additionally, the final mechanomyograph design was easier to use and adjust than the original design and fit a wider range of hand sizes. The final design also reduced the frequency of adjustments and the time needed for adjustments, facilitating data collection during a surgical procedure.

Accuracy and Precision of Three Acceleromyographs, Three Electromyographs and a Mechanomyograph Measuring the Train-of-Four Ratio in the Absence of Neuromuscular Blocking Drugs.

BACKGROUND: The accuracy and precision of currently available, widely used acceleromyograph and electromyograph neuromuscular blockade monitors have not been well studied. In addition, the normalization of the train-of-four ratio from acceleromyography (train-of-four ratio [T4/T1] divided by the baseline train-of-four ratio) has not been validated in comparison to mechanomyography. METHODS: Enrolled patients had surgery under general anesthesia with a supraglottic airway and without any neuromuscular blocking drugs. Three acceleromyograph monitors, three electromyograph monitors and a mechanomyograph built in our laboratory were tested. Most patients had an electromyograph and the mechanomyograph on one arm and a third monitor on the contralateral arm. Train-of-four ratios were collected every 12-20 seconds for the duration of the anesthetic. At least 1,000 train-of-four ratios were recorded for each device. Gauge repeatability and reproducibility analysis was performed. RESULTS: Twenty-eight patients were enrolled. In total, 9,498 train-of-four ratio measurements were collected. Since no neuromuscular blocking drugs were used, the expected train-of-four ratio was 1.0. All of the acceleromyograph monitors produced overshoot in the train-of-four ratio (estimated means 1.10-1.13) and substantial variability (gauge standard deviations 0.07-0.18). Normalization of the train-of-four ratio measured by acceleromyography improved the estimated mean for each device (0.97-1.0) but the variability was not improved (gauge standard deviations 0.06-0.17). The electromyograph and the mechanomyograph monitors produced minimal overshoot (estimated means 0.99-1.01) and substantially less variation (gauge standard deviations 0.01-0.02). For electromyography and mechanomyography, 0.3% of all train-of-four ratios were outside of the range of 0.9-1.1. For acceleromyography, 27% to 51% of normalized train-of-four ratios were outside of the range of 0.9-1.1. CONCLUSION: Three currently available acceleromyograph monitors produced overshoot and substantial variability that could be clinically significant. Normalization corrected the overshoot in the average results but did not reduce the wide variability. Three electromyograph monitors measured the train-of-four ratio with minimal overshoot and variability, similar to a mechanomyograph.

Comparison of a Modern Digital Mechanomyograph to a Mechanomyograph Utilizing an Archival Grass Force Transducer.

BACKGROUND: Mechanomyography is the traditional gold standard research technique for quantitative assessment of neuromuscular blockade. Mechanomyography directly measures the isometric force generated by the thumb in response to ulnar nerve stimulation. Researchers must construct their own mechanomyographs since commercial instruments are no longer available. A mechanomyograph was constructed, and its performance was compared against an archival mechanomyography system from the 1970s that utilized an FT-10 Grass force transducer, hypothesizing that train-of-four ratios recorded on each device would be equivalent. METHODS: A mechanomyograph was constructed using 3D-printed components and modern electronics. An archival mechanomyography system was assembled from original components, including an FT-10 Grass force transducer. Signal digitization for computerized data collection was utilized instead of the original paper strip chart recorder. Both devices were calibrated with standard weights to demonstrate linear voltage response curves. The mechanomyographs were affixed to opposite arms of patients undergoing surgery, and the train-of-four ratio was measured during the onset and recovery from rocuronium neuromuscular blockade. RESULTS: Calibration measurements exhibited a positive linear association between voltage output and calibration weights with a linear correlation coefficient of 1.00 for both mechanomyography devices. The new mechanomyograph had better precision and measurement sensitivity than the archival system: 5.3 mV versus 15.5 mV and 1.6 mV versus 5.7 mV, respectively (P < 0.001 for both). A total of 767 pairs of train-of-four ratio measurements obtained from eight patients had positive linear association (R 2 = 0.94; P < 0.001). Bland-Altman analysis resulted in bias of 3.8% and limits of agreement of -13% and 21%. CONCLUSIONS: The new mechanomyograph resulted in similar train-of-four ratio measurements compared to an archival mechanomyography system utilizing an FT-10 Grass force transducer. These results demonstrated continuity of gold standard measurement of neuromuscular blockade spanning nearly 50 yr, despite significant changes in the instrumentation technology.

A Dose-finding Study of Sugammadex for Reversal of Rocuronium in Cardiac Surgery Patients and Postoperative Monitoring for Recurrent Paralysis.

BACKGROUND: The dose of sugammadex recommended by the manufacturer for reversal of rocuronium is 2 mg/kg when the train-of-four count is 2 or more and 4 mg/kg when it is less than 2 but there is a posttetanic count of at least 1. The purpose of this dose-finding study was to titrate sugammadex to produce a train-of-four ratio 0.9 or greater at the conclusion of cardiac surgery, and to continue monitoring neuromuscular blockade in the intensive care unit to identify recurrent paralysis. The hypothesis was that many patients would require less than the recommended dose of sugammadex, but that some would require more, and that recurrent paralysis would not occur. METHODS: Neuromuscular blockade was monitored using electromyography during cardiac surgery. Administration of rocuronium was at the discretion of the anesthesia care team. During sternal closure, sugammadex was titrated in 50-mg increments every 5 min until a train-of-four ratio 0.9 or greater was obtained. Neuromuscular blockade was monitored with electromyography in the intensive care unit until sedation was discontinued before extubation or for a maximum of 7 h. RESULTS: Ninety-seven patients were evaluated. The dose of sugammadex required to achieve a train-of-four ratio of 0.9 or greater varied from 0.43 to 5.6 mg/kg. There was a statistically significant relationship between the depth of neuromuscular blockade and the sugammadex dose required for reversal, but there was a large variation in dose required at any depth of neuromuscular blockade. Eighty-four of 97 patients (87%) required less than the recommended dose, and 13 (13%) required more. Two patients required additional sugammadex administration for recurrent paralysis. CONCLUSIONS: When sugammadex was titrated to effect, the dose was usually less than the recommended dose, but it was more in some patients. Therefore, quantitative twitch monitoring is essential for ascertaining that adequate reversal has taken place after sugammadex administration. Recurrent paralysis was observed in two patients.

Nighttime Extubation Does Not Increase Risk of Reintubation, Length of Stay, or Mortality: Experience of a Large, Urban, Teaching Hospital.

BACKGROUND: In the intensive care unit (ICU), extubation failure has been associated with greater resource utilization and worsened clinical outcomes. Most recently, nighttime extubation (NTE) has been reported as a risk factor for increased ICU and hospital mortality. We hypothesized that, in a large, urban, university-affiliated hospital with multidisciplinary assessment for extubation, rigorously protocolized extubation algorithms, and expert airway managers available at all times of day for assessment of high-risk extubations, NTE would not confer additional risk of adverse clinical outcomes. METHODS: This was a retrospective cohort study of mechanically ventilated adults at a single university-affiliated hospital. NTE was defined as occurring between 7:00 PM and 6:59 AM the following day. All data were extracted from the institution's electronic medical record. Multivariable regression analyses were used to assess associations between NTE and reintubation, ICU and hospital length of stay (LOS), and mortality with adjustments for demographic and clinical covariates defined a priori. Palliative, unplanned, and routine postoperative extubations were excluded in sensitivity analyses. RESULTS: Of 2241 patients, 204 of 2241 (9.1%) underwent NTE. The rates of reintubation (NTE 6.9% versus daytime extubation [DTE] 12.4%; adjusted odds ratio [95% confidence interval {CI}], 0.78 [0.43-1.41]; P = .41) and in-hospital mortality (NTE 3.4% versus DTE 5.9%; adjusted odds ratio [95% CI], 0.72 [0.28-1.84]; P = .49) were not found to differ. NTE, compared to DTE, was associated with shorter duration of mechanical ventilation (median [interquartile range], 1 [0-1] days vs 2 [1-4] days; adjusted ratio of geometric means [RGMs] [95% CI], 0.64 [0.54-0.70]; P < .001), ICU (2 [1-5] days vs 4 [2-10] days; adjusted RGMs [95% CI], 0.65 [0.57-0.75]; P < .001), and hospital LOS (6 [3-18] days vs 13 [6-25] days; adjusted RGMs [95% CI], 0.64 [0.56-0.74]; P < .001). These results were unchanged in sensitivity analyses. CONCLUSIONS: Patients who underwent NTE were not at increased risk of reintubation or in-hospital mortality. In addition, NTE was associated with a shortened duration of mechanical ventilation and hospital LOS. In health care systems with similar critical care delivery models, NTE may coincide with reduced resource utilization in appropriately selected patients.

Effects of breast density and compression on normal breast tissue hemodynamics through breast tomosynthesis guided near-infrared spectral tomography.

Optically derived tissue properties across a range of breast densities and the effects of breast compression on estimates of hemoglobin, oxygen metabolism, and water and lipid concentrations were obtained from a coregistered imaging system that integrates near-infrared spectral tomography (NIRST) with digital breast tomosynthesis (DBT). Image data were analyzed from 27 women who underwent four IRB approved NIRST/DBT exams that included fully and mildly compressed breast acquisitions in two projections­craniocaudal (CC) and mediolateral-oblique (MLO)­and generated four data sets per patient (full and moderate compression in CC and MLO views). Breast density was correlated with HbT (r=0.64, p=0.001), water (r=0.62, p=0.003), and lipid concentrations (r=?0.74, p<0.001), but not oxygen saturation. CC and MLO views were correlated for individual subjects and demonstrated no statistically significant differences in grouped analysis. Comparison of compressed and uncompressed imaging demonstrated a significant decrease in oxygen saturation under compression (58% versus 50%, p=0.04). Mammographic breast density categorization was correlated with measured optically derived properties.

Calibration and optimization of 3D digital breast tomosynthesis guided near infrared spectral tomography.

Calibration of a three-dimensional multimodal digital breast tomosynthesis (DBT) x-ray and non-fiber based near infrared spectral tomography (NIRST) system is challenging but essential for clinical studies. Phantom imaging results yielded linear contrast recovery of total hemoglobin (HbT) concentration for cylindrical inclusions of 15 mm, 10 mm and 7 mm with a 3.5% decrease in the HbT estimate for each 1 cm increase in inclusion depth. A clinical exam of a patient's breast containing both benign and malignant lesions was successfully imaged, with greater HbT was found in the malignancy relative to the benign abnormality and fibroglandular regions (11 µM vs. 9.5 µM). Tools developed improved imaging system characterization and optimization of signal quality, which will ultimately improve patient selection and subsequent clinical trial results.

Digital Breast Tomosynthesis guided Near Infrared Spectroscopy: Volumetric estimates of fibroglandular fraction and breast density from tomosynthesis reconstructions.

A multimodality system combining a clinical prototype digital breast tomosynthesis with its imaging geometry modified to facilitate near-infrared spectroscopic imaging has been developed. The accuracy of parameters recovered from near-infrared spectroscopy is dependent on fibroglandular tissue content. Hence, in this study, volumetric estimates of fibroglandular tissue from tomosynthesis reconstructions were determined. A kernel-based fuzzy c-means algorithm was implemented to segment tomosynthesis reconstructed slices in order to estimate fibroglandular content and to provide anatomic priors for near-infrared spectroscopy. This algorithm was used to determine volumetric breast density (VBD), defined as the ratio of fibroglandular tissue volume to the total breast volume, expressed as percentage, from 62 tomosynthesis reconstructions of 34 study participants. For a subset of study participants who subsequently underwent mammography, VBD from mammography matched for subject, breast laterality and mammographic view was quantified using commercial software and statistically analyzed to determine if it differed from tomosynthesis. Summary statistics of the VBD from all study participants were compared with prior independent studies. The fibroglandular volume from tomosynthesis and mammography were not statistically different (p=0.211, paired t-test). After accounting for the compressed breast thickness, which were different between tomosynthesis and mammography, the VBD from tomosynthesis was correlated with (r =0.809, p<0.001), did not statistically differ from (p>0.99, paired t-test), and was linearly related to, the VBD from mammography. Summary statistics of the VBD from tomosynthesis were not statistically different from prior studies using high-resolution dedicated breast computed tomography. The observation of correlation and linear association in VBD between mammography and tomosynthesis suggests that breast density associated risk measures determined for mammography are translatable to tomosynthesis. Accounting for compressed breast thickness is important when it differs between the two modalities. The fibroglandular volume from tomosynthesis reconstructions is similar to mammography indicating suitability for use during near-infrared spectroscopy.

Sensitivity of MRI-guided near-infrared spectroscopy clinical breast exam data and its impact on diagnostic performance.

In this study, data from breast MRI-guided near infrared spectroscopy (NIRS) exams delivered to 44 patients scheduled for surgical resection (ending in 16 benign and 28 malignant diagnoses) were analyzed using a spatial sensitivity metric to quantify the adequacy of the optical measurements for interrogating the tumor region of interest, as derived from the concurrent MRI scan. Along with positional sensitivity, the incorporation of spectral priors and the selection of an appropriate regularization parameter in the image reconstruction were considered, and found to influence the diagnostic accuracy of the recovered images. Once optimized, the MRI/NIRS data was able to differentiate the malignant from benign lesions through both total hemoglobin (p = 0.0037) and tissue optical index (p = 0.00019), but required the relative spatial sensitivity of the optical measurement data to each lesion to be above 1%. Spectral constraints implemented during the reconstruction were required to obtain statistically significant diagnostic information from images of H2O, lipids, and Tissue Optical Index (TOI). These results confirm the need for optical systems that have homogenous spatial coverage of the breast while still being able to accommodate the normal range of breast sizes.

Anthropomorphic breast phantoms with physiological water, lipid, and hemoglobin content for near-infrared spectral tomography.

Breast mimicking tissue optical phantoms with sufficient structural integrity to be deployed as stand-alone imaging targets are developed and successfully constructed with biologically relevant concentrations of water, lipid, and blood. The results show excellent material homogeneity and reproducibility with inter- and intraphantom variability of 3.5 and 3.8%, respectively, for water and lipid concentrations ranging from 15 to 85%. The phantoms were long-lasting and exhibited water and lipid fractions that were consistent to within 5% of their original content when measured 2 weeks after creation. A breast-shaped three-compartment model of adipose, fibroglandular, and malignant tissues was created with water content ranging from 30% for the adipose simulant to 80% for the tumor. Mean measured water content ranged from 30% in simulated adipose to 73% in simulated tumor with the higher water localized to the tumor-like material. This novel heterogeneous phantom design is composed of physiologically relevant concentrations of the major optical absorbers in the breast in the near-infrared wavelengths that should significantly improve imaging system characterization and optimization because the materials have stand-alone structural integrity and can be readily molded into the sizes and shapes of tissues commensurate with clinical breast imaging.

Pilot study assessment of dynamic vascular changes in breast cancer with near-infrared tomography from prospectively targeted manipulations of inspired end-tidal partial pressure of oxygen and carbon dioxide.

The dynamic vascular changes in the breast resulting from manipulation of both inspired end-tidal partial pressure of oxygen and carbon dioxide were imaged using a 30 s per frame frequency-domain near-infrared spectral (NIRS) tomography system. By analyzing the images from five subjects with asymptomatic mammography under different inspired gas stimulation sequences, the mixture that maximized tissue vascular and oxygenation changes was established. These results indicate maximum changes in deoxy-hemoglobin, oxygen saturation, and total hemoglobin of 21, 9, and 3%, respectively. Using this inspired gas manipulation sequence, an individual case study of a subject with locally advanced breast cancer undergoing neoadjuvant chemotherapy (NAC) was analyzed. Dynamic NIRS imaging was performed at different time points during treatment. The maximum tumor dynamic changes in deoxy-hemoglobin increased from less than 7% at cycle 1, day 5 (C1, D5) to 17% at (C1, D28), which indicated a complete response to NAC early during treatment and was subsequently confirmed pathologically at the time of surgery.

A digital x-ray tomosynthesis coupled near infrared spectral tomography system for dual-modality breast imaging.

A Near Infrared Spectral Tomography (NIRST) system has been developed and integrated into a commercial Digital Breast Tomosynthesis (DBT) scanner to allow structural and functional imaging of breast in vivo. The NIRST instrument uses an 8-wavelength continuous wave (CW) laser-based scanning source assembly and a 75-element silicon photodiode solid-state detector panel to produce dense spectral and spatial projection data from which spectrally constrained 3D tomographic images of tissue chromophores are produced. Integration of the optical imaging system into the DBT scanner allows direct co-registration of the optical and DBT images, while also facilitating the synergistic use of x-ray contrast as anatomical priors in optical image reconstruction. Currently, the total scan time for a combined NIRST-DBT exam is ~50s with data collection from 8 wavelengths in the optical scan requiring ~42s to complete. The system was tested in breast simulating phantoms constructed using intralipid and blood in an agarose matrix with a 3 cm x 2 cm cylindrical inclusion at 1 cm depth from the surface. Diffuse image reconstruction of total hemoglobin (HbT) concentration resulted in accurate recovery of the lateral size and position of the inclusion to within 6% and 8%, respectively. Use of DBT structural priors in the NIRST reconstruction process improved the quantitative accuracy of the HbT recovery, and led to linear changes in imaged versus actual contrast, underscoring the advantages of dual-modality optical imaging approaches. The quantitative accuracy of the system can be further improved with independent measurements of scattering properties through integration of frequency or time domain data.

Semi-automated segmentation and classification of digital breast tomosynthesis reconstructed images.

Digital breast tomosynthesis (DBT) is a limited-angle tomographic x-ray imaging technique that reduces the effect of tissue superposition observed in planar mammography. An integrated imaging platform that combines DBT with near infrared spectroscopy (NIRS) to provide co-registered anatomical and functional imaging is under development. Incorporation of anatomic priors can benefit NIRS reconstruction. In this work, we provide a segmentation and classification method to extract potential lesions, as well as adipose, fibroglandular, muscle and skin tissue in reconstructed DBT images that serve as anatomic priors during NIRS reconstruction. The method may also be adaptable for estimating tumor volume, breast glandular content, and for extracting lesion features for potential application to computer aided detection and diagnosis.