Japanese Regulatory Considerations for Interoperability of Medical Devices.

With the rapid technological innovations of the Internet of Things (IoT), the situation surrounding medical devices and medical systems has been changing. Interoperable medical devices-medical devices capable of interoperating in a clinically significant way with other medical devices-have been developed, and interoperable medical systems consisting of two or more interconnected interoperable medical devices are being used in clinical settings. However, general points that need to be considered to ensure safe and effective interoperability have yet to be fully established in Japan. A research project (FY2019-FY2021) to discuss issues associated with ensuring safe and effective interoperability was commissioned by the Japan Agency for Medical Research and Development. A pivotal aspect identified in that project is how to manage the sharing of data and information among interoperable medical devices from different manufacturers. Characteristics and timestamps of data and information need to be exchanged between interoperable medical devices. Risks associated with interoperable devices should be managed in a manner appropriate to the characteristics and the intended use of the interoperable medical devices. In this review, we summarize the aspects of data and information that this study group judged were important to consider for ensuring safety and effective interoperability.

Rotors anchored by refractory islands drive torsades de pointes in an experimental model of electrical storm.

BACKGROUND: Electrical storm (ES) is a life-threatening emergency in patients at high risk of ventricular tachycardia/ventricular fibrillation (VF), but the pathophysiology and molecular basis are poorly understood. OBJECTIVE: The purpose of this study was to explore the electrophysiological substrate for experimental ES. METHODS: A model was created by inducing chronic complete atrioventricular block in defibrillator-implanted rabbits, which recapitulates QT prolongation, torsades des pointes (TdP), and VF episodes. RESULTS: Optical mapping revealed island-like regions with action potential duration (APD) prolongation in the left ventricle, leading to increased spatial APD dispersion, in rabbits with ES (defined as ≥3 VF episodes/24 h). The maximum APD and its dispersion correlated with the total number of VF episodes in vivo. TdP was initiated by an ectopic beat that failed to enter the island and formed a reentrant wave and perpetuated by rotors whose centers swirled in the periphery of the island. Epinephrine exacerbated the island by prolonging APD and enhancing APD dispersion, which was less evident after late Na+ current blockade with 10 µM ranolazine. Nonsustained ventricular tachycardia in a non-ES rabbit heart with homogeneous APD prolongation resulted from multiple foci with an electrocardiographic morphology different from TdP driven by drifting rotors in ES rabbit hearts. The neuronal Na+-channel subunit NaV1.8 was upregulated in ES rabbit left ventricular tissues and expressed within the myocardium corresponding to the island location in optically mapped ES rabbit hearts. The NaV1.8 blocker A-803467 (10 mg/kg, intravenously) attenuated QT prolongation and suppressed epinephrine-evoked TdP. CONCLUSION: A tissue island with enhanced refractoriness contributes to the generation of drifting rotors that underlies ES in this model. NaV1.8-mediated late Na+ current merits further investigation as a contributor to the substrate for ES.

MR Imaging of Hair and Scalp for the Evaluation of Androgenetic Alopecia.

PURPOSE: Although androgenetic alopecia (AGA) is a common cause of hair loss, little is known regarding the magnetic resonance imaging (MRI) of the AGA or scalp. This study aimed to analyze whether MRI for hair and scalp (MRH) can evaluate anatomical changes in the scalp caused by AGA. METHODS: Twenty-seven volunteers were graded for the severity of AGA using the Hamilton-Norwood Scale (HNS), commonly used classification system. All subjects underwent MRH; two radiologists independently analyzed the images. As a quantitative measurement, the number of hair follicles was analyzed and compared with the HNS. As a qualitative analysis, each MRH scan was visually graded in terms of the severity of alopecia, using a 4-point MR severity score. The scores were compared with the HNS. RESULTS: The volunteers were divided into two groups of 12 and 15 males without and with AGA at their vertex, respectively. Inter-observer agreements for the hair count and the MR severity score were excellent. The mean hair count on MRI in the normal group was significantly higher than that in the AGA group (P < 10-4). The MR severity score in the AGA group was significantly more severe than that in the control group (P < 10-4). In terms of the presence or absence of thinning hair, the MR severity score was consistent with the HNS determined by a plastic surgeon in 96% of cases. MR severity scores of clinically moderate AGA cases were significantly lower than those of severe cases (P = 0.022). CONCLUSION: MRH could depict scalp anatomy showing a clear difference between AGA and normal scalps, in both hair count and subjective visual assessment. The MR severity score was in good agreement with the clinical stages by HNS. The results support the potential of MRH as a promising imaging technique for analyzing healthy and pathological scalps.

Quantitative analysis of the anatomical changes in the scalp and hair follicles in androgenetic alopecia using magnetic resonance imaging.

BACKGROUND: Although the structural changes of the scalp in androgenetic alopecia (AGA) have been reported, these changes have been poorly understood. It is expected that modern MRI would visualize the scalp anatomy in vivo. This study aimed to explore whether AGA causes (a) changes in the thickness of the scalp, (b) anatomical changes in the hair follicles, and (c) changes in the signal intensity of MRI. MATERIALS AND METHODS: Twenty-seven volunteers underwent MRI for hair and scalp (MRH) and were categorized into two according to the Hamilton-Norwood Scale: the "AGA group" and the "normal group." Two radiologists analyzed the thickness and signal intensity of the scalp, and the depth of hair follicles. These measurements were compared between the two groups. RESULTS: The thickness of the hypodermis and the entire scalp was significantly thinner in the AGA group than in the control group. The AGA group had significantly shallower depth of hair follicles and relative depth of the hair follicles to that of the entire scalp than the normal group. The hypodermis showed higher signal intensity in the AGA group than the normal group. CONCLUSION: MRH allowed noninvasive visualization of the scalp anatomy and demonstrated the thinner nature of the entire scalp and hypodermis, along with the shallower depth of the hair follicles in the AGA group in comparison to the normal group. Additionally, MRH demonstrated the increased MR signal intensity in the scalp associated with AGA. MRH may be a promising new method for quantitative and objective analyses of AGA.

Interaction of phase singularities on the spiral wave tail: reconsideration of capturing the excitable gap.

The action mechanism of stimulation toward spiral waves (SWs) owing to the complex excitation patterns that occur just after point stimulation has not yet been experimentally clarified. This study sought to test our hypothesis that the effect of capturing excitable gap of SWs by stimulation can also be explained as the interaction of original phase singularity (PS) and PSs induced by the stimulation on the wave tail (WT) of the original SW. Phase variance analysis was used to quantitatively analyze the postshock PS trajectories. In a two-dimensional subepicardial layer of Langendorff-perfused rabbit hearts, optical mapping was used to record the excitation pattern during stimulation. After a SW was induced by S1-S2 shock, single biphasic point stimulation S3 was applied. In 70 of the S1-S2-S3 stimulation episodes applied on 6 hearts, the original PS was clearly observed just before the S3 point stimulation in 37 episodes. Pairwise PSs were newly induced by the S3 in 20 episodes. The original PS collided with the newly induced PSs in 16 episodes; otherwise, they did not interact with the original PS. SW shift occurred most efficiently when the S3 shock was applied at the relative refractory period, and PS shifted in the direction of the WT. In conclusion, quantitative tracking of PS clarified that stimulation in desirable conditions induces pairwise PSs on WT and that the collision of PSs causes SW shift along the WT. The results of this study indicate the importance of the interaction of shock-induced excitation with the WT for effective stimulation. NEW & NOTEWORTHY The quantitative analysis of spiral wave dynamics during stimulation clarified the action mechanism of capturing the excitable gap, i.e., the induction of pairwise phase singularities on the wave tail and spiral wave shift along the wave tail as a result of these interactions. The importance of the wave tail for effective stimulation was revealed.

Mechanism of Traumatic Brain Injury at Distant Locations After Exposure to Blast Waves: Preliminary Results from Animal and Phantom Experiments.

Purpose Primary blast-induced traumatic brain injury (bTBI) is the least understood of the four phases of blast injury. Distant injury induced by the blast wave, on the opposite side from the wave entry, is not well understood. This study investigated the mechanism of distant injury in bTBI. Materials and Methods Eight 8-week-old male Sprague-Dawley rats were divided into two groups: group 1 served as the control group and did not receive any shock wave (SW) exposure; group 2 was exposed to SWs (12.5 ± 2.5 MPa). Propagation of SWs within a brain phantom was evaluated by visualization, pressure measurement, and numerical simulation. Results Intracerebral hemorrhage near the ignition site and elongation of the distant nucleus were observed, despite no apparent damage between the two locations in the animal experiment. Visualization, pressure measurement, and numerical simulation indicated the presence of complex wave dynamics accompanying a sudden increase in pressure, followed by negative pressure in the phantom experiment. Conclusion A local increase in pressure above the threshold caused by interference of reflection and rarefaction waves in the vicinity of the brain-skull surface may cause distant injury in bTBI.

Detection Algorithm of Phase Singularity Using Phase Variance Analysis for Epicardial Optical Mapping Data.

OBJECTIVE: Spiral reentry is a recognized cause of tachycardia. Detection and tracking of the spiral core are essential for understanding the spiral wave dynamics. The core of the spiral corresponds to a phase singularity (PS), which can be identified in an optical mapping image by a kernel convolution method. However, because of a large number of false positives, this method cannot automatically and stably track the core of sustaining spiral reentry in optical mapping data. METHOD: We developed a new PS detection algorithm that quantifies the variance of phase values in a phase map and identifies the position of PS as its peak. RESULTS: In comparison with the kernel convolution method, our method improved the precision of detecting a single sustaining spiral wave core from 73.1% to 99.8%. The precision of the proposed method for virtual-electrode-polarization-induced multiple PSs detections was also higher than the convolutional method. CONCLUSION: The proposed method detects PS by finding the peaks in the phase variance distribution of cardiac optical mapping image. It improved the precision of the core detection of the spiral wave in cardiac optical mapping images in comparison with the conventional kernel convolution method. SIGNIFICANCE: The proposed method will reveal the spiral wave dynamics in optical mapping images better than existing approaches. The objective analysis method of a spiral wave is important for understanding the mechanisms and dynamics of serious heart arrhythmias.

Pulsed Laser-induced Liquid Jet System for Treatment of Sellar and Parasellar Tumors: Safety Evaluation.

OBJECTIVE: The pulsed laser-induced liquid jet (LILJ) system is an emerging surgical instrument intended to assist both maximal removal of the lesion and functional maintenance through preservation of fine vessels and minimal damage to the surrounding tissue. The system ejects the minimum required amount of pulsed water through a handy bayonet-shaped catheter. We have already shown a significant increase in removal rate, in addition to a noteworthy reduction of intraoperative blood loss and procedure time in the treatment of large pituitary and skull base tumors in a single-institution series. The present study evaluated the safety of the system in multiple institutions. METHODS: The study included 46 patients, 29 men and 17 women (mean age: 59.1 years) who underwent microsurgical/endoscopic resection of lesions in or in the vicinity of the pituitary fossa through the transsphenoidal approach between October 2011 and June 2012 at six institutions. The histologic diagnoses were pituitary adenoma (31 cases), meningioma (4), craniopharyngioma (3), cavernous angioma (2), and Rathke cyst cleft (1). Lesion volume ranged from 2.0 to 30.4 cm³ (mean: 3.7 cm³). Cavernous sinus invasion was observed in 11 cases and suprasellar extension in 29 cases. RESULTS: Preservation of intralesional arteries (diameter: 150 µm) was achieved in all situations in > 80% of cases. Intended surgical steps were achieved except for some restrictions in motion due to the use of an optical quartz fiber. No complications occurred directly related to the use of the device. CONCLUSIONS: The LILJ system can be used for safe removal of lesions in or in the vicinity of the pituitary fossa.

Hypothermia in victims of the great East Japan earthquake: a survey in Miyagi prefecture.

OBJECTIVE: A survey was conducted to describe the characteristics of patients treated for hypothermia after the Great East Japan Earthquake. METHODS: Written questionnaires were distributed to 72 emergency medical hospitals in Miyagi Prefecture. Data were requested regarding inpatients with a temperature less than 36ºC admitted within 72 hours after the earthquake. The availability of functional heating systems and the time required to restore heating after the earthquake were also documented. RESULTS: A total of 91 inpatients from 13 hospitals were identified. Tsunami victims comprised 73% of the patients with hypothermia. Within 24 hours of the earthquake, 66 patients were admitted. Most patients with a temperature of 32ºC or higher were treated with passive external rewarming with blankets. Discharge without sequelae was reported for 83.3% of patients admitted within 24 hours of the earthquake and 44.0% of those admitted from 24 to 72 hours after the earthquake. Heating systems were restored within 3 days of the earthquake at 43% of the hospitals. CONCLUSIONS: Hypothermia in patients hospitalized within 72 hours of the earthquake was primarily due to cold-water exposure during the tsunami. Many patients were successfully treated in spite of the post-earthquake disruption of regional social infrastructure.

Reliability of telecommunications systems following a major disaster: survey of secondary and tertiary emergency institutions in Miyagi Prefecture during the acute phase of the 2011 Great East Japan Earthquake.

INTRODUCTION: Telecommunication systems are important for sharing information among health institutions to successfully provide medical response following disasters. HYPOTHESIS/PROBLEM: The aim of this study was to clarify the problems associated with telecommunication systems in the acute phase of the Great East Japan Earthquake (March 11, 2011). METHODS: All 72 of the secondary and tertiary emergency hospitals in Miyagi Prefecture were surveyed to evaluate the telecommunication systems in use during the 2011 Great Japan Earthquake, including satellite mobile phones, multi-channel access (MCA) wireless systems, mobile phones, Personal Handy-phone Systems (PHS), fixed-line phones, and the Internet. Hospitals were asked whether the telecommunication systems functioned correctly during the first four days after the earthquake, and, if not, to identify the cause of the malfunction. Each telecommunication system was considered to function correctly if the hospital staff could communicate at least once in every three calls. RESULTS: Valid responses were received from 53 hospitals (73.6%). Satellite mobile phones functioned correctly at the highest proportion of the equipped hospitals, 71.4%, even on Day 0. The MCA wireless system functioned correctly at the second highest proportion of the equipped hospitals. The systems functioned correctly at 72.0% on Day 0 and at 64.0% during Day 1 through Day 3. The main cause of malfunction of the MCA wireless systems was damage to the base station or communication lines (66.7%). Ordinary (personal or general communication systems) mobile phones did not function correctly at any hospital until Day 2, and PHS, fixed-line phones, and the Internet did not function correctly at any area hospitals that were severely damaged by the tsunami. Even in mildly damaged areas, these systems functioned correctly at <40% of the hospitals during the first three days. The main causes of malfunction were a lack of electricity (mobile phones, 25.6%; the Internet, 54.8%) and damage to the base stations or communication lines (the Internet, 38.1%; mobile phones, 56.4%). CONCLUSION: Results suggest that satellite mobile phones and MCA wireless systems are relatively reliable and ordinary systems are less reliable in the acute period of a major disaster. It is important to distribute reliable disaster communication equipment to hospitals and plan for situations in which hospital telecommunications systems do not function.

Tissue dissection before direct manipulation to the pathology with pulsed laser-induced liquid jet system in skull base surgery--preservation of fine vessels and maintained optic nerve function.

BACKGROUND: Most difficulties in skull base tumor removal are generally caused by adhesion of feeding arteries to the vital structures and cranial nerves. Water jet technology provides tissue dissectability with preservation of fine blood vessels both in experimental and clinical situations. However problems still remain regarding whether tumor removal with preservation of peripheral nerve function is possible or not. This clinical investigation evaluated functional preservation of peripheral nerves and dissectability with a newly developed pulsed laser-induced liquid jet (LILJ) system under intraoperative electrophysiological monitoring. METHODS: The LILJ system was used to treat 21 patients with skull base tumors manifesting as severe visual disturbance through the extended transsphenoidal approach. The LILJ system consists of a bayonet-shaped catheter incorporating a jet generator, and total weight is around 7 g. Intraoperative visual evoked potential (VEP), and pre/postoperative conventional visual assessments were investigated. RESULTS: Precise dissections of the tumor were obtained, resulting in gross total removal in 19 of 21 patients. Two patients with meningiomas with tight adhesion to the origin of the lenticulostriate arteries had small remnants. Of the 21 patients, 16 showed immediate improvement on intraoperative VEP, 2 had no change, and 3 had prolonged latency, which required intermittent suspension of procedure. A total of 20 patients and 40 eyes showed good recovery at discharge, and all patients evaluated had recovered good visual status. CONCLUSIONS: The LILJ system can achieve safe and optimal removal with functional preservation of optic nerves, probably because of the high resistance of the arachnoidal sheath and fine vascular tissue.

Single camera system for multi-wavelength fluorescent imaging in the heart.

Optical mapping has been a powerful method to measure the cardiac electrophysiological phenomenon such as membrane potential(V(m)), intracellular calcium(Ca(2+)), and the other electrophysiological parameters. To measure two parameters simultaneously, the dual mapping system using two cameras is often used. However, the method to measure more than three parameters does not exist. To exploit the full potential of fluorescence imaging, an innovative method to measure multiple, more than three parameters is needed. In this study, we present a new optical mapping system which records multiple parameters using a single camera. Our system consists of one camera, custom-made optical lens units, and a custom-made filter wheel. The optical lens units is designed to focus the fluorescence light at filter position, and form an image on camera's sensor. To obtain optical signals with high quality, efficiency of light collection was carefully discussed in designing the optical system. The developed optical system has object space numerical aperture(NA) 0.1, and image space NA 0.23. The filter wheel was rotated by a motor, which allows filter switching corresponding with needed fluorescence wavelength. The camera exposure and filter switching were synchronized by phase locked loop, which allow this system to record multiple fluorescent signals frame by frame alternately. To validate the performance of this system, we performed experiments to observe V(m) and Ca(2+) dynamics simultaneously (frame rate: 125fps) with Langendorff perfused rabbit heart. Firstly, we applied basic stimuli to the heart base (cycle length: 500ms), and observed planer wave. The waveforms of V(m) and Ca(2+) show the same upstroke synchronized with cycle length of pacing. In addition, we recorded V(m) and Ca(2+) signals during ventricular fibrillation induced by burst pacing. According to these experiments, we showed the efficacy and availability of our method for cardiac electrophysiological research.

Clinical implications of intraoperative infrared brain surface monitoring during superficial temporal artery-middle cerebral artery anastomosis in patients with moyamoya disease.

OBJECT: Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving cerebral blood flow (CBF). Symptomatic cerebral hyperperfusion is a potential complication of this procedure, but its treatment is contradictory to that for ischemia. Because intraoperative techniques to detect hyperperfusion are still lacking, the authors performed intraoperative infrared monitoring in moyamoya disease using a novel infrared imaging system. METHODS: During superficial temporal artery-middle cerebral artery anastomosis in 25 patients (26 hemispheres) with moyamoya disease, the authors monitored the brain surface temperature intraoperatively with the IRIS-V infrared imaging system. The average gradation value change (indicating temperature change) was calculated using commercial software. Magnetic resonance imaging, MR angiography, and N-isopropyl-p-[(123)I]iodoamphetamine SPECT studies were performed routinely before and within 10 days after surgery. RESULTS: Patency of bypass, detailed local hemodynamics, and changes in cortical surface temperature around the anastomosis site were well recognized by the IRIS-V infrared imaging system in all cases. In the present study, 10 patients suffered transient neurological symptoms accompanied by an increase in CBF around the anastomosis site, recognized as symptomatic hyperperfusion. The increase in temperature was significantly higher in these patients. Intensive blood pressure control was undertaken, and free-radical scavengers were administered. No patient in the present study suffered a permanent neurological deficit. CONCLUSIONS: Although the present method does not directly monitor surface CBF, temperature rise around the anastomosis site during surgery might be an indicator of postoperative hyperperfusion. Prospective evaluation with a larger number of patients is necessary to validate this technique.

Intraoperative infrared brain surface blood flow monitoring during superficial temporal artery-middle cerebral artery anastomosis in patients with childhood moyamoya disease.

OBJECTIVE: To monitor patency of the bypass and to accomplish comprehensive visualized evaluation of brain surface hemodynamics in childhood moyamoya patients, we performed intraoperative monitoring using novel infrared imaging system. MATERIALS AND METHODS: Intraoperative monitoring of brain surface blood flow by IRIS V infrared imaging system has been conducted during superficial temporal artery-middle cerebral artery anastomosis on seven sides of five pediatric patients with moyamoya disease (man/woman = 2:3, 7-8 years old). The range of recipient artery was 0.7-0.8 mm (average 0.75 mm). Magnetic resonance imaging and magnetic resonance angiography were performed routinely before and after surgery. CONCLUSIONS: In all cases, patency of bypass, as well as detailed local hemodynamics and changes of brain surface temperature distribution could be evaluated. Intraoperative infrared system will be a feasible monitoring not only for noninvasive intraoperative evaluation of bypass patency but also for local hemodynamics even in patients with childhood moyamoya disease.

Intraoperative infrared brain surface blood flow monitoring during superficial temporal artery-middle cerebral artery anastomosis in a patient with moyamoya disease: clinical implication of the gradation value in postoperative clinical course--a case report.

BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is a safe and effective treatment for moyamoya disease. Symptomatic cerebral hyperperfusion is a potential complication of this procedure, especially in adult cases. Accurate diagnosis of postoperative hyperperfusion is important because its treatment is contradictory to that for ischemia. Intraoperative techniques to detect hyperperfusion are still lacking. METHODS: We performed intraoperative infrared (IR) brain surface monitoring in a 36-year-old man who underwent left STA-MCA anastomosis. FINDINGS: IR monitoring not only detected the patency of bypass, as also confirmed by conventional Doppler sonography and postoperative magnetic resonance angiography, but also delineated the local brain surface hemodynamics after revascularization. Analysis of gradation value disclosed an abnormal increase in brain surface cerebral blood flow (indirectly indicated as a temperature change) after removal of the temporary clip. The patient suffered from transient right upper extremity numbness and dysarthria due to focal hyperperfusion from postoperative days 2 through 6. Intensive blood pressure control completely relieved his symptoms, and he was discharged without neurologic deficit. CONCLUSIONS: Intraoperative brain surface monitoring by IR imaging may be useful to predict cerebral hyperperfusion after revascularization surgery for moyamoya disease. Further evaluation with a larger number of patients is necessary to validate this technique.

Development of optical mapping system with real-time feedback stimulation in the heart.

Recent studies showed that electrical stimuli in the excitable gaps during ventricular fibrillation (VF) are important for defibrillation requiring low electrical energy. We developed an optical mapping system that measures action potentials and controls the timings and sites of electrical stimulus to verify the effectiveness of electrical stimulation in the excitable gaps. In this paper, the time delay of feedback algorithms with our optical mapping system was evaluated and the feedback stimulation protocols were operated using isolated rabbit hearts. We optically mapped electrical activity from a surface of Langendorff-perfused rabbit hearts stained with a voltage sensitive dye using high-speed video cameras. Acquiring image data triggered a timing pulse after 5.5ms using LED. In the experiment using isolated rabbit hearts, the timing delay was 10.2 ms. The velocity and direction of wave propagation was calculated in real-time using two reference points on a field of view. The two electrical stimulating points was selected by the action potentials on electrical stimulation points. The electrical shock was delivered on the point that was triggered earlier than the other point.