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The aim of this study was to assess the utility of an actuator-driven pulsed water jet (ADPJ) as a hardness-dependent carious dentin removal device by using different outputs. Thirty-six plane surface dental caries samples were treated with the ADPJ at 150, 200, and 250 voltage (12 teeth each). The Knoop hardness number (KHN) and Ca/P mass ratio were measured at 70 μm from the deepest point of the removing groove. Furthermore, three other teeth samples were manually treated with the ADPJ at the three above mentioned voltages (one tooth each) for 1 min. The KHN and Ca/P mass ratio were measured at 70 μm from the surface of the residual dentin part. In both the KHN and Ca/P mass ratio, higher residual dentin depended on the applied voltage of ADPJ. The ADPJ enabled the removal of softened carious dentin in an applied voltage-dependent manner.

Object Pulsed water jet is an emerging surgical instrumentation intended to achieve both maximal lesion resection and functional maintenance through preservation of fine vessels and minimal damage to the surrounding tissue. The piezo actuator-driven pulsed water jet (ADPJ) is a new technology that can deliver a precisely controlled uniform and efficient pulsed water jet with minimum water flow. The present study evaluated the ADPJ system in preclinical animal studies in the swine brain, and investigated breaking strength, one of the parameters for mechanical properties, to elucidate the mechanism of tissue selectivity for tissue dissection by the water jet. Methods This system consisted of a pump chamber driven by a piezo actuator, a stainless steel tube, and a nozzle (internal diameter: 0.15 mm). The water was supplied at 6 ml/min. The relationship between input voltage (3-25 V at 400 Hz) and peak pressure was measured using a pressure sensor through a sensing hole. Temporal profile of dissection depth during moving application was evaluated using gelatin brain phantom and swine brain. The dissected specimens were evaluated histologically. The mechanical property (breaking strength) of swine brain was measured by a compact table-top universal tester. Results Peak pressure increased linearly with increase in the input voltage, which reflected dissection depth in both the gelatin brain phantom and swine brain. Small arteries were preserved, and minimum damage to surrounding tissues occurred. The breaking strength of arachnoid membrane (0.12 ± 0.014 MPa) was significantly higher compared to gray matter (0.030 ± 0.010 MPa) and white matter (0.056 ± 0.009 MPa) (p < 0.05). The breaking strength of gray matter corresponded to that of 3 wt% gelatin, and that of white matter corresponded to a value between those of 3.5 and 4 wt% gelatin, and the dissection depth seemed to be estimated by 3-4 wt% gelatin. Conclusion The present study suggests that the ADPJ system has the potential to achieve accurate tissue dissection with preservation of blood vessels in neurosurgery. The difference in breaking strength may explain the tissue selectivity between brain parenchyma and tissue protected by the arachnoid membrane.

The advent of image-activated cell sorting and imaging-based cell picking has advanced our knowledge and exploitation of biological systems in the last decade. Unfortunately, they generally rely on fluorescent labeling for cellular phenotyping, an indirect measure of the molecular landscape in the cell, which has critical limitations. Here we demonstrate Raman image-activated cell sorting by directly probing chemically specific intracellular molecular vibrations via ultrafast multicolor stimulated Raman scattering (SRS) microscopy for cellular phenotyping. Specifically, the technology enables real-time SRS-image-based sorting of single live cells with a throughput of up to ~100 events per second without the need for fluorescent labeling. To show the broad utility of the technology, we show its applicability to diverse cell types and sizes. The technology is highly versatile and holds promise for numerous applications that are previously difficult or undesirable with fluorescence-based technologies., Most current cell sorting methods are based on fluorescence detection with no imaging capability. Here the authors generate and use Raman image-activated cell sorting with a throughput of around 100 events per second, providing molecular images with no need for labeling.

The main objectives of critical care of severe traumatic brain injury(TBI)are the prevention and treatment of intracranial hypertension and secondary brain insults, preservation of cerebral perfusion pressure, and optimization of cerebral oxygenation. The critical care management of severe TBI will be discussed with a focus on the monitoring and avoidance or minimization of secondary brain insults, with emphasis on understanding the underlying physiology and pathophysiology. The evolution of critical care of severe traumatic brain injury will also be discussed along with the accumulating knowledge and experience.

Objective We developed an actuator-driven pulsed water jet (ADPJ) device to achieve maximal lesion dissection with minimal risk of normal structural damage. Despite the unique dissection characteristics, there is a risk of dissemination of tissue dispersion; however, there is no established method to quantify the dispersion. Hence, this study aimed to assess the factors associated with dispersion and propose a simple experimental method using spectrophotometry to evaluate the degree of dispersion in a wet field. Results Methylene blue-stained brain phantom gelatin was immersed in a chamber with distilled water solution and dissected with an ADPJ. The dispersed gelatin solution was stirred and warmed to dissolve. The absorbance of the solution was measured spectrophotometrically. First, a reference standard curve was constructed to confirm the relationship between the absorbance and the amount of the dispersed gelatin. A clear proportional correlation was observed, which indicated that absorbance measurements can help evaluate the amount of dispersion. Using this method, we revealed that a high dissection force, insufficient suction, and inappropriate long distance between the nozzle tip and the target were associated with increased dispersion. This method might constitute a versatile and reliable approach to evaluate dispersion and aid in the development of surgical devices.

Objective To identify the outcome of patients with sepsis using high-frequency blood pressure data. Materials and methods This retrospective observational study was conducted at a university hospital ICU (derivation study) and at two urban hospitals (validation study) with data from adult sepsis patients who visited the centers during the same period. The area under the curve (AUC) of blood pressure falling below threshold was calculated. The predictive 90-day mortality (primary endpoint) area under threshold (AUT) and critical blood pressure were calculated as the maximum area under the curve of the receiver operating characteristic curve (AUCROC) and the threshold minus average AUT (derivation study), respectively. For the validation study, the derived 90-day mortality AUCROC (using critical blood pressure) was compared with Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score (SAPS) II, Acute Physiology and Chronic Health Evaluation (APACHE) II, and APACHE III. Results Derivation cohort (N = 137): the drop area from the mean blood pressure of 70 mmHg at 24-48 hours most accurately predicted 90-day mortality [critical blood pressure, 67.8 mmHg; AUCROC, 0.763; 95% confidence interval (CI), 0.653-0.890]. Validation cohort (N = 141): the 90-day mortality AUCROC (0.776) compared with the AUCROC for SOFA (0.711), SAPSII (0.771), APACHE II (0.745), and APACHE III (0.710) was not significantly different from the critical blood pressure 67.8 mmHg (P = 0.420). Conclusion High-frequency arterial blood pressure data of the period and extent of blood pressure depression can be useful in predicting the clinical outcomes of patients with sepsis.

Intelligent image-activated cell sorting (iIACS) is a machine-intelligence technology that performs real-time intelligent image-based sorting of single cells with high throughput. iIACS extends beyond the capabilities of fluorescence-activated cell sorting (FACS) from fluorescence intensity profiles of cells to multidimensional images, thereby enabling high-content sorting of cells or cell clusters with unique spatial chemical and morphological traits. Therefore, iIACS serves as an integral part of holistic single-cell analysis by enabling direct links between population-level analysis (flow cytometry), cell-level analysis (microscopy), and gene-level analysis (sequencing). Specifically, iIACS is based on a seamless integration of high-throughput cell microscopy (e.g., multicolor fluorescence imaging, bright-field imaging), cell focusing, cell sorting, and deep learning on a hybrid software-hardware data management infrastructure, enabling real-time automated operation for data acquisition, data processing, intelligent decision making, and actuation. Here, we provide a practical guide to iIACS that describes how to design, build, characterize, and use an iIACS machine. The guide includes the consideration of several important design parameters, such as throughput, sensitivity, dynamic range, image quality, sort purity, and sort yield; the development and integration of optical, microfluidic, electrical, computational, and mechanical components; and the characterization and practical usage of the integrated system. Assuming that all components are readily available, a team of several researchers experienced in optics, electronics, digital signal processing, microfluidics, mechatronics, and flow cytometry can complete this protocol in ~3 months.

Objective We developed an actuator-driven pulsed water jet device (ADPJ) for flexible neuroendoscopy to achieve effective tissue dissection with vasculature preservation. Although flexibility is a strong advantage for minimally invasiveness, the effect of the ductile curvature on the dissection profiles remains unknown. The purpose of this study was to clarify the impact of the curvature change of the ADPJ connecting tube on the dissection safety and efficacy. Results Three ADPJ connecting tubes with different inner diameters (1.0, 0.75, 0.5 mm) were used to dissect the brain phantom. They were bent at 3 angles: 0°, 60°, and 120°. The dissection profiles were evaluated using the mean depth and coefficient of variation (CV) for efficacy and safety, respectively.The larger inner diameter connecting tube dissected more deeply. The dissection depth was not changed regardless of the curvature degree in each tube. There was no significant difference in CVs regardless of inner diameter and curvature. The ductile curvature of the flexible neuroendoscope did not affect the efficacy and safety of the ADPJ dissection profile. Among the numerous instruments, tube-formed devices, including suction and injecting devices such as ADPJ, can be used safely and effectively without flexibility-related limitations.

Background While hand and ultrasonic scalers are the primary tools used for the removal of dental calculus in periodontal treatment, many studies have shown that they also damage the enamel surface. We have developed a novel actuator-driven pulsed water jet (ADPJ) system, which has the ability to selectively remove materials depending on their stiffness. Considering the different material properties between teeth and dental calculus, it might be possible to develop the ADPJ to remove dental calculus without damage to the tooth’s enamel surface using a suitable jet pressure. Therefore, the aim of this study was to assess the effectiveness of the ADPJ in removing dental calculus, and the surface features of the teeth after its use. Methods A total of 93 artificial teeth coated with artificial dental calculus were examined in this study. The weights of 90 teeth were measured before and after the use of ADPJ, which had an applied voltage setting of 150, 200, or 240 V. The three remaining teeth were instrumented with a conventional hand scaler, ultrasonic scaler, or ADPJ (set at 240 V). Damage to the artificial tooth surfaces was evaluated using 5% Evans blue dye under an optical microscope. Furthermore, apatite pellets, which are utilized as experimental substitutes for natural teeth, were assessed after the use of ADPJ and both conventional scalers. Results The ADPJ significantly reduced the amount of artificial calculus, and the removal rate was dependent on the applied voltage. No damage was observed on the surface of the artificial tooth and apatite pellet following the use of ADPJ, in contrast to the conventional scalers. Conclusions The results of this study demonstrate the in vitro effectiveness of ADPJ in the removal of dental calculus, without causing damage to tooth surfaces.

The advent of intelligent image-activated cell sorting (iIACS) has enabled high-throughput intelligent image-based sorting of single live cells from heterogeneous populations. iIACS is an on-chip microfluidic technology that builds on a seamless integration of a high-throughput fluorescence microscope, cell focuser, cell sorter, and deep neural network on a hybrid software-hardware data management architecture, thereby providing the combined merits of optical microscopy, fluorescence-activated cell sorting (FACS), and deep learning. Here we report an iIACS machine that far surpasses the state-of-the-art iIACS machine in system performance in order to expand the range of applications and discoveries enabled by the technology. Specifically, it provides a high throughput of ∼2000 events per second and a high sensitivity of ∼50 molecules of equivalent soluble fluorophores (MESFs), both of which are 20 times superior to those achieved in previous reports. This is made possible by employing (i) an image-sensor-based optomechanical flow imaging method known as virtual-freezing fluorescence imaging and (ii) a real-time intelligent image processor on an 8-PC server equipped with 8 multi-core CPUs and GPUs for intelligent decision-making, in order to significantly boost the imaging performance and computational power of the iIACS machine. We characterize the iIACS machine with fluorescent particles and various cell types and show that the performance of the iIACS machine is close to its achievable design specification. Equipped with the improved capabilities, this new generation of the iIACS technology holds promise for diverse applications in immunology, microbiology, stem cell biology, cancer biology, pathology, and synthetic biology.

Background Pulsed water jet dissection is an emerging surgical method for achieving maximal resection of a lesion and postoperative function preservation. We aimed to clarify liver damage and long-term results after liver resection using a novel surgical device, piezo actuator-driven pulsed water jet (ADPJ), in a rat model.Methods We categorizedSprague–Dawley rats into four groups and subjected themto sham operation or liver resection using an ADPJ, an ultrasonic aspirator (UA), or a radio knife. At 1, 3, 7, 14, 28, and 56 days postoperatively, we euthanizedfive rats from each group after collecting blood samples and harvested residual livers.We measured serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutamate dehydrogenase (GLDH) concentrations. Morphological characteristics and resection surfaces were assessed by hematoxylin–eosin staining.ResultsOn day 1, serum AST and ALT levels were significantly lower with an ADPJ than with an UA and a radio knife (AST: ADPJ vs. UA, PPPPPPPPConclusionsLiver damage afterliver resection was markedly less with an ADPJ than with an UA or a radio knife. Furthermore, the liver recovered faster after an ADPJ.

There is limited information about acute phase renal replacement therapy (RRT) for maintenance hemodialysis patients after the onset of cerebrovascular disease. This study aimed to investigate which modality of renal replacement therapy is currently selected in practice. We conducted a mail-based survey in 317 dialysis facilities that were certified by three academic societies that focus on dialysis, neurology, and neurosurgery in Japan. We received responses from 103 facilities (32.5%). In cases of cerebral infarction (CI) and intracerebral hemorrhage (ICH), more than 80% of the facilities selected only intermittent RRT, and 22.3% (CI)/8.7% (ICH) of the facilities selected intermittent HD which is the same setting in normal conditions. Although continuous hemodiafiltration and peritoneal dialysis are recommended in the Japanese guidelines, these were selected in only a few facilities: 16.5% and 0% in CI, 16.5% and 1% in ICH, respectively. RRT on the day of onset tended to be avoided, irrespective of the duration following the last HD session. Furthermore, physicians preferred to modify anticoagulants and reduce dialysis performance in the acute phase. This questionnaire survey uncovered a gap between guidelines and actual practice, even in hospitals accredited as educational facility, which is a novel and important finding. Further studies with larger sample sizes are needed to determine the optimal modality of RRT for the acute phase of cerebrovascular disease.

Objective Maximum resection with minimum damage to normal structures is required for a better clinical outcome. Several efficient surgical devices such as the Cavitron ultrasonic surgical aspirator are available. Our group developed the actuator-driven pulsed water jet (ADPJ) to dissect soft tissue with vessel preservation. Although these devices are very effective for resection, tumor seeding is a potential risk. The present study investigated the control of splashing during ADPJ use. We demonstrate the effect of additional water flow around the instrument tip to veil the splashing. Methods Pulsed water jet was ejected from the tip of the ADPJ nozzle. Effects of ADPJ parameters such as input voltage, suction pressure, and distance between the nozzle and the target (standoff distance) on the amount of splashing were analyzed. Methylene blue solution was ejected on photo paper, gelatin brain phantom, and porcine brain harvested and subsequently immersed into physiologic saline to quantify the amount of splashing. Results High-input voltage and a long standoff distance had significant correlations with large amounts of splashing (r > 0.5; p Conclusions The veil effect of additional water flow is important to reduce splashing during ADPJ use and can minimize the potential risk of dissemination and enhance the safety of the ADPJ.

Traumatic injury caused by explosive or blast events is traditionally divided into four mechanisms: primary, secondary, tertiary, and quaternary blast injury. The mechanisms of blast-induced traumatic brain injury (bTBI) are biomechanically distinct and can be modeled in both in vivo and in vitro systems. The primary bTBI injury mechanism is associated with the response of brain tissue to the initial blast wave. Among the four mechanisms of bTBI, there is a remarkable lack of information regarding the mechanism of primary bTBI. On the other hand, 30 years of research on the medical application of shock waves (SWs) has given us insight into the mechanisms of tissue and cellular damage in bTBI, including both air-mediated and underwater SW sources. From a basic physics perspective, the typical blast wave consists of a lead SW followed by shock-accelerated flow. The resultant tissue injury includes several features observed in primary bTBI, such as hemorrhage, edema, pseudo-aneurysm formation, vasoconstriction, and induction of apoptosis. These are well-described pathological findings within the SW literature. Acoustic impedance mismatch, penetration of tissue by shock/bubble interaction, geometry of the skull, shear stress, tensile stress, and subsequent cavitation formation are all important factors in determining the extent of SW-induced tissue and cellular injury. In addition, neuropsychiatric aspects of blast events need to be taken into account, as evidenced by reports of comorbidity and of some similar symptoms between physical injury resulting in bTBI and the psychiatric sequelae of post-traumatic stress. Research into blast injury biophysics is important to elucidate specific pathophysiologic mechanisms of blast injury, which enable accurate differential diagnosis, as well as development of effective treatments. Herein we describe the requirements for an adequate experimental setup when investigating blast-induced tissue and cellular injury; review SW physics, research, and the importance of engineering validation (visualization/pressure measurement/numerical simulation); and, based upon our findings of SW-induced injury, discuss the potential underlying mechanisms of primary bTBI.

In recent years, instances of neurotrauma in the elderly have been increasing. This article addresses the clinical characteristics, management strategy, and outcome in elderly patients with traumatic brain injury (TBI). Falls to the ground either from standing or from heights are the most common causes of TBI in the elderly, since both motor and physiological functions are degraded in the elderly. Subdural, contusional and intracerebral hematomas are more common in the elderly than the young as the acute traumatic intracranial lesion. High frequency of those lesions has been proposed to be associated with increased volume of the subdural space resulting from the atrophy of the brain in the elderly. The delayed aggravation of intracranial hematomas has been also explained by such anatomical and physiological changes present in the elderly. Delayed hyperemia/hyperperfusion may also be a characteristic of the elderly TBI, although its mechanisms are not fully understood. In addition, widely used pre-injury anticoagulant and antiplatelet therapies may be associated with delayed aggravation, making the management difficult for elderly TBI. It is an urgent issue to establish preventions and treatments for elderly TBI, since its outcome has been remained poor for more than 40 years.

In clipping surgery for aneurysmal subarachnoid hemorrhage (aSAH), critical steps include clot removal and dissection of aneurysms without premature rupture or brain injuries. To pursue this goal, a piezo actuator-driven pulsed water jet (ADPJ) system was introduced in this study. This study included 42 patients, who suffered aSAH and underwent clipping surgery. Eleven patients underwent surgery with the assistance of the ADPJ system (ADPJ group). In the other 31 patients, surgery was performed without the ADPJ system (Control group). The ADPJ system was used for clot removal and aneurysmal dissection. The clinical impact of the ADPJ system was judged by comparing the rate of premature rupture, degree of clot removal, and clinical outcomes. Intraoperatively, a premature rupture was encountered in 18.2 and 25.8% of cases in the ADPJ and control groups, respectively. Although the differences were not statistically significant, intraoperative observation suggested that the ADPJ system was effective in clot removal and dissection of aneurysms in a safe manner. Computed tomography scans indicated the achievement of higher degrees of clot removal, especially when the ADPJ system was used for cases with preoperative clot volumes of more than 25 ml (p = 0.047, Mann-Whitney U test). Clinical outcomes, including incidence of postoperative brain injury or symptomatic vasospasm, were similar in both groups. We described our preliminary surgical results using the ADPJ system for aSAH. Although further study is needed, the ADPJ system was considered a safe and effective tool for clot removal and dissection of aneurysms.

Background: Chronic subdural hematoma (CSDH) is a common neurosurgical disease. A subset of patients with CSDH may exhibit underlying spontaneous intracranial hypotension (SIH). Bilateral CSDH has a causal relationship with SIH, but there is no known causal relationship between unilateral CSDH and SIH.Case description: We encountered four cases of unilateral CSDH due to SIH. The patients' age ranged between 44 and 64 years; there were three males and one female. All patients presented with headache as their initial symptom, and then became comatose. Computed tomography demonstrated unilateral CSDH and transtentorial herniation in all patients. Treatments were emergency epidural blood patch (EBP) and evacuation of CSDH. The site of cerebrospinal fluid leak could not be identified in three patients; therefore, EBP was performed at upper and lower spine. All patients recovered from SIH; however, one patient experienced poor outcome due to Duret hemorrhage and ischemic complications of transtentorial herniation. Cranial asymmetry was present in all four patients, and unilateral CSDH was located on the side of the most curved cranial convexity.Conclusions: Unilateral CSDH, asymmetric cranial morphology, and transtentorial herniation in relatively young patients may indicate underlying SIH.

A totally soft organic subdural electrode has been developed by embedding an array of poly(3,4-ethylenedioxythiophene)-modified carbon fabric (PEDOT-CF) into the polyvinyl alcohol (PVA) hydrogel substrate. The mesh structure of the stretchable PEDOT-CF allowed stable structural integration with the PVA substrate. The electrode performance for monitoring electrocorticography (ECoG) was evaluated in saline solution, on ex vivo brains, and in vivo animal experiments using rats and porcines. It was demonstrated that the large double-layer capacitance of the PEDOT-CF brings low impedance at the frequency of brain wave including epileptic seizures, and PVA hydrogel substrate minimized the contact impedance on the brain. The most important unique feature of the hydrogel-based ECoG electrode was its shape conformability to enable tight adhesion even to curved, grooved surface of brains by just being placed. In addition, since the hydrogel-based electrode is totally organic, the simultaneous ECoG-fMRI measurements could be conducted without image artifacts, avoiding problems induced by conventional metallic electrodes.

Background and Study Aims Various minimally invasive approaches are used in neurosurgery. Surgeons must perform nondynamic fine movements in a narrow corridor, so specially designed surgical devices are essential. Unsophisticated instruments may pose potential hazards. The purpose of this study was to assess the factors associated with muscle fatigue during minimally invasive neurosurgery and to investigate whether physical stress can be reduced by refining the devices used. Material and Methods Four physical aspects of a handpiece were investigated: torque of conduits (0.20, 0.28, and 0.37 kgf*cm), shape of hand grip (five types), angle of the nozzle (0, 20, and 40 degrees), and weight balance (neutral, proximal, and distal). To evaluate muscle fatigue, surface electromyography was recorded from the extensor carpi radialis muscle and flexor carpi radialis muscle during a geometric tracing task. The maximum voluntary contraction (MVC) of each muscle and %MVC (muscle contraction during a task/MVC × 100) were used as the indexes of muscle fatigue. Results The shape of the hand grip significantly reduced %MVC, which is associated with muscle fatigue. The torque of conduits and angle of the nozzle tended to reduce muscle fatigue but not significantly. Weight balance did not affect muscle fatigue. Based on these results, we made two refined models: model α (torque of conduits 0.2 kgf*cm, angle of nozzle 20 degrees, neutral balance, hand grip with a 2.9 × 2.0-cm oval section with angled finger rest), and model β (torque of conduits 0.2 kgf*cm, angle of nozzle 20 degrees, neutral balance, hand grip with a 2.9-cm round section with a curved finger rest). The %MVC was significantly decreased with both types (p Conclusions The geometrically refined surgical device can improve muscle load during surgery and reduce the surgeon's physical stress, thus minimizing the risk of complications.

Shock waves (SW) have been applied to a variety of medical treatments. Recent studies have focused on applications within microenvironments. On the other hand, blast-induced traumatic injury (bTBI) became a social problem after the Iraq and Afghanistan conflict, and SW is gaining attention to understand the mechanism of primary bTBI. This paper reports a preliminary experimental result of SW propagation in simulated biomedical materials for understanding mechanism of both potential complication of medical application of SW within the cranium and bTBI. SW, generated by detonating of a 10 mg silver azide (AgN3) pellet, was interacted with a brain model using simulated biomedical materials. The process of SW interaction with a brain model was visualized by shadowgraph method and recorded by a high-speed video camera. The pressure history in a brain model was measured by a polyvinylidene fluoride needle hydrophone. The present experiment showed occurrence of complex wave front at specific location within the chamber and indicated the importance of understanding SW propagation effect when applying SW above certain overpressure. We will also summarize current research of complication of SW medical application and also bTBI.

A procedure to retract brain tissue is a fundamental and important procedure for accessing a lesioned part located in the deep brain in neurosurgery. In order to provide a training environment to novice surgeons, a prototype of a surgical simulator which can simulate the retraction of soft tissue utilizing the advantage of an encountered-type haptic interface using MR fluid has been developed. In this paper, a force controller for displaying a retracting force of soft biological tissue with a spatula is proposed. The haptic interface was connected with a simple FEM (Finite Element Method) based simulator and displayed the computed reaction force from virtual tissue by using the proposed controller.

The high-speed liquid (water) jet has distinctive characteristics in surgical applications, such as tissue dissection without thermal damage and small blood vessel preservation, that make it advantageous over more conventional instruments. The continuous pressurized jet has been used since the first medical application of water jets to liver surgery in the 1980s, but exhibited drawbacks partly related to the excess water supply required and unsuitability for application to microsurgical instruments intended for deep, narrow lesions (endoscopic instrumentation and catheters) due to limitations in miniaturization of the device. To solve these issues, we initiated work on the pulsed micro-liquid jet. The idea of the pulsed micro-liquid jet originated from the observation of tissue damage by shock/bubble interactions during extracorporeal shock wave lithotripsy and evolved into experimental application for recanalization of cerebral embolisms in the 1990s. The original method of generating the liquid jet was based on air bubble formation and microexplosives as the shock wave source, and as such could not be applied clinically. The air bubble was replaced by a holmium:yttrium-aluminum-garnet (Ho:YAG) laser-induced bubble. Finally, the system was simplified and the liquid jet was generated via irradiation from the Ho:YAG laser within a liquid-filled tubular structure. A series of investigations revealed that this pulsed laser-induced liquid jet (LILJ) system has equivalent dissection and blood vessel preservation characteristics, but the amount of liquid usage has been reduced to less than 2 $$\upmu $$ l per shot and can easily be incorporated into microsurgical, endoscopic, and catheter devices. As a first step in human clinical studies, we have applied the LILJ system for the treatment of skull base tumors through the transsphenoidal approach in 9 patients (7 pituitary adenomas and 2 chordomas), supratentorial glioma (all high grade glioma) in 8 patients, including one with fine perforating vessel involvement, and cerebrovascular disease (1 arteriovenous malformation and 2 intracerebral hemorrhages) in 3 patients. Precise dissection and mass reduction of the tumor were obtained in all tumor cases except for one chordoma with significant fibrosis. Small arteries down to 100 $$\upmu \hbox {m}$$ were preserved, allowing subsequent microsurgical devascularization. Veins were also preserved occasionally. The arachnoid membrane and the tumor capsule were resistant to the LILJ except for one case with prolonged exposure. No complications related to use of the LILJ system were observed. No disturbance of the surgical field by splashing, aerosol, or dissemination of pathological tissue occurred with placement of the optimal suction system. The Ho:YAG LILJ system enhances the advantages of commercialized pressure-driven continuous liquid jet instrumentation in terms of small vessel preservation and accessibility in confined spaces for minimally invasive neurosurgery, and solves some of the drawbacks involved with excessive liquid use and size.

In surgery of epilepsy, a patient's cranium is opened for intracranial electroencephalogram (iEEG) measurement or electrical stimulation to treat a part of a brain causing seizures [1]. Conventionally, intracranial metal electrodes with a silicone rubber substrate have been widely used in iEEG measurements during surgery. However, the substrate of the electrode is stiff and needs to be pressed down to fit on the surface of the brain, which increases the tissue damage during the insertion into in a deep sulcus called a longitudinal cerebral fissure or a Silvian fissure. Besides, the low transparency of the electrode substrate decreases the immediate recognition of the diseased area, and the lack of permeability of that also cause damage to the brain in long term treatment including an implantation of the electrode. Herein, a flexible intracranial electrode using a hydrogel as a substrate was developed [2]. A soft carbon fabric electrode was embedded in a hydrogel composed of poly (vinyl alcohol) (PVA). The PVA hydrogel has excellent flexibility, biocompatibility, water content, and hydrophilicity, which leads to well adhesion and conformability to the brain. Moreover, the transparency of PVA hydrogel is expected to improve the visibility of the brain under the substrate and its permeability ensure adequate fluid delivery. Carbon fabric electrodes were fabricated by cutting the electrodes and lead wires out of the fabric and applying an insulation coating. The non-insulated electrode surface was coated with conductive particle polymer poly (3,4-ethylenedioxythiophene) (PEDOT) to increase the surface area and increase the electrical capacity. This process is to prevent electrolysis from occurring during electrical stimulation[3]. A gel precursor solution was prepared by dissolving PVA in distilled water and adding dimethyl sulfoxide (DMSO). The electrodes were embedded in the precursor solution and gelated by repeated freezing and thawing cycles. DMSO provided an uniform and clear gel, and to avoid its irritation, the obtained gel was soaked and washed well in saline. Figures 1 shows the electrodes placed on the brain model. While the conventional electrodes with silicone substrate hardly followed the shape of the object (Figure 1a), the electrodes with hydrogel substrate followed the object well (Figure 1b). The object was not clear to observe through the conventional silicone substrate, and that substrate did not swell the water droplet placed on the surface (Figure 1c). In contrast, the hydrogel-based substrate was clear after the adhesion onto the brain model, and the water droplets placed on the surface were spread over the entire surface and adsorbed to the hydrogel-based substrate. These results indicated that electrodes with a hydrogel substrate could adhere well to the brain surface while minimizing damage to the tissue, and allowing observation of the affected area during surgery. Our developed electrode with soft, hydrophilic, and soft hydrogel substrate were promising device for the treatment of epilepsy, overcoming the conventional problems and leading to new medical approach. References [1] S. Noachtar, I. Borggraefe, “Epilepsy surgery: A critical review”, Epilepsy Behav., 15, 66-72, (2009) [2] S. Oribe, S. Yoshida, S. Kusama, S. Osawa, A. Nakagawa, M. Iwasaki, T. Tominaga, and M. Nishizawa, “Hydrogel-Based Organic Subdural Electrode with High Conformability to Brain Surface”, Sci. Rep., 9, 13379, (2019). [3] S. Yoshida, K. Sumomozawa, K. Nagamine, and M. Nishizawa, “Hydrogel Microchambers Integrated with Organic Electrode for Efficient Electrical Stimulation of Human iPSC-Derived Cardiomyocytes”, Macromol. Biosci., 19, e1900060, (2019) Figure 1

A fundamental challenge of biology is to understand the vast heterogeneity of cells, particularly how cellular composition, structure, and morphology are linked to cellular physiology. Unfortunately, conventional technologies are limited in uncovering these relations. We present a real-time machine intelligence technology based on a radically new architecture that realizes real-time image-based intelligent cell search and sorting at an unprecedented rate. The technology integrates high-throughput cell imaging, cell focusing, and cell sorting on a hybrid software-hardware data management infrastructure, enabling real-time automated operation for data acquisition, data processing, decision making, and actuation. Specifically, we use it to demonstrate real-time sorting of microalgal and blood cells based on intracellular protein localization and cell-cell interaction from large heterogeneous populations for studying photosynthesis and atherothrombosis, respectively. Our technology is highly versatile and expected to enable machine-based scientific discovery in biological, pharmaceutical, and medical sciences.

Here, we discuss a case of carotid blowout syndrome successfully treated with endovascular parent artery occlusion. A 71-year-old woman underwent treatment for esophageal cancer resection, followed by 50-Gy radiotherapy, 19 years prior. Due to local recurrence, she underwent 66- and 72-Gy radiation treatments at 2 and 4 years after the initial treatment, respectively. Afterward, tracheostomy and enterostomy were performed. This time, she was transported to our emergency department because of acute eruptive bleeding from the tracheal tube. As her vitals indicated shock, emergency endovascular treatment was performed. Digital subtraction angiography revealed that the common carotid artery in the left-sided of the neck had a pseudoaneurysm extruding to the pharyngeal cavity, which was considered to be the lesion responsible for the acute rupture. She was diagnosed as having carotid blowout syndrome. Balloon test occlusion showed that the cross flow via the anterior and posterior communicating arteries was sufficient, so parent artery occlusion was chosen for bleeding control. Carotid bifurcation was preserved to keep the collateral circulation via the external carotid artery. The patient was discharged 22 days after treatment, without any neurological deficits. Although injured vessel removal with high-flow bypass was an ideal treatment to achieve bleeding control without ischemic complication, endovascular treatment can be an efficient second-best treatment. To minimize the risk of late ischemic complications, flow preservation via carotid bifurcation might be important.

Actuator-driven pulsed water-jet (ADPJ) dissection is an emerging surgical method for dissecting tissue without heat and mechanical injury to vessels. We elucidated the mechanical properties of the piezo ADPJ and evaluated its usefulness and safety in coronary artery bypass grafting procedures. The relationship between the input voltage (10-100 V) and peak pressure of the pulsed water jet was evaluated. The tissue strengths of swine internal thoracic and coronary arteries and the surrounding tissues were measured to assure tissue-selective dissection. Internal thoracic arteries were harvested by conventional electric cautery and the water jet in four swine, and eight coronary arteries surrounded by myocardium were attempted to be exposed with the water jet. The dissected specimens were histologically evaluated. The peak pressure of the pulsed water jet was positively correlated with the input voltage (R 2 = 0.9984, P

Paroxysmal sympathetic hyperactivity (PSH) is a distinct syndrome of episodic sympathetic hyperactivities following severe acquired brain injury, characterized by paroxysmal transient fever, tachycardia, hypertension, tachypnea, excessive diaphoresis and specific posturing. PSH remains to be an under-recognized condition with a diagnostic pitfall especially in the intensive care unit (ICU) settings due to the high prevalence of concomitant diseases that mimic PSH. A consensus set of diagnostic criteria named PSH-Assessment Measure (PSH-AM) has been developed recently, which is consisted of two components: a diagnosis likelihood tool derived from clinical characteristics of PSH, and a clinical feature scale assigned to the severity of each sympathetic hyperactivity. We herein present a case series of patients with PSH who were diagnosed and followed by using PSH-AM in our tertiary institutional medical and surgical ICU between April 2015 and March 2017 in order to evaluate the clinical efficacy of PSH-AM. Among 394 survivors of 521 patients admitted with acquired brain injury defined as acute brain injury at all levels of severity regardless of the presence of altered consciousness, including traumatic brain injury, stroke, infectious disease, and encephalopathy, 6 patients (1.5%) were diagnosed as PSH by using PSH-AM. PSH-AM served as a useful scoring system for early objective diagnosis, assessment of severity, and serial evaluation of treatment efficacy in the management of PSH in the ICU settings. In conclusion, critical care clinicians should consider the possibility of PSH and can use PSH-AM as a useful diagnostic and guiding tool in the management of PSH.

According to WHO, about 10 million new cases of thrombotic disorders are diagnosed worldwide every year. Thrombotic disorders, including atherothrombosis (the leading cause of death in the US and Europe), are induced by occlusion of blood vessels, due to the formation of blood clots in which aggregated platelets play an important role. The presence of aggregated platelets in blood may be related to atherothrombosis (especially acute myocardial infarction) and is, hence, useful as a potential biomarker for the disease. However, conventional high-throughput blood analysers fail to accurately identify aggregated platelets in blood. Here we present an in vitro on-chip assay for label-free, single-cell image-based detection of aggregated platelets in human blood. This assay builds on a combination of optofluidic time-stretch microscopy on a microfluidic chip operating at a high throughput of 10 000 blood cells per second with machine learning, enabling morphology-based identification and enumeration of aggregated platelets in a short period of time. By performing cell classification with machine learning, we differentiate aggregated platelets from single platelets and white blood cells with a high specificity and sensitivity of 96.6% for both. Our results indicate that the assay is potentially promising as predictive diagnosis and therapeutic monitoring of thrombotic disorders in clinical settings.