Neural Dielet 2.0: A 128-Channel 2mm×2mm Battery-Free Neural Dielet Merging Simultaneous Multi-Channel Transmission through Multi-Carrier Orthogonal Backscatter.

Miniaturization of wireless neural-recording systems enables minimally-invasive surgery and alleviates the rejection reactions for implanted brain-computer interface (BCI) applications. Simultaneous massive-channel recording capability is essential to investigate the behaviors and inter-connections in billions of neurons. In recent years, battery-free techniques based on wireless power transfer (WPT) and backscatter communication have reduced the sizes of neural-recording implants by battery eliminating and antenna sharing. However, the existing battery-free chips realize the multi-channel merging in the signal-acquisition circuits, which leads to large chip area, signal attenuation, insufficient channel number or low bandwidth, etc. In this work, we demonstrate a 2mm×2mm battery-free neural dielet, which merges 128 channels in the wireless part. The neural dielet is fabricated with 65nm CMOS process, and measured results show that: 1) The proposed multi-carrier orthogonal backscatter technique achieves a high data rate of 20.16Mb/s and an energy efficiency of 0.8pJ/bit. 2) A self-calibrated direct digital converter (SC-DDC) is proposed to fit the 128 channels in the 2mm×2mm die, and then the all-digital implementation achieves 0.02mm2 area and 9.87µW power per channel.

Quantitative evaluation of CTP derived time-density alterations versus CTP for collateral status prediction with stroke.

BACKGROUND AND OBJECTIVES: Collateral status is a pivotal determinant of clinical outcomes in acute ischemic stroke (AIS); however, its evaluation can be challenging. We investigated the predictive value of CT perfusion (CTP) derived time and density alterations versus CTP for collateral status prediction in AIS. METHODS: Consecutive patients with anterior circulation occlusion within 24 h were retrospectively included. Time-density curves of the CTP specified ischemic core, penumbra, and the corresponding contralateral unaffected brain were obtained. The collateral status was dichotomised into robust (4-5 scores) and poor (0-3 scores) using multiphase collateral scoring, as described by Menon et al.. Receiver operating characteristic curves and multivariable regression analysis were performed to assess the predictive ability of CTP-designated tissue time and density alterations, CTP for robust collaterals, and favourable outcomes (mRS score of 0-2 at 90 days). RESULTS: One-hundred patients (median age, 68 years; interquartile range, 57-80 years; 61 men) were included. A smaller ischemic core, shorter peak time delay, lower peak density decrease, lower cerebral blood volume ratio, and cerebral blood flow ratio in the CTP specified ischemic core were significantly associated with robust collaterals (PFDR ≤ 0.004). The peak time delay demonstrated the highest diagnostic value (AUC, 0.74; P < 0.001) with 66.7 % sensitivity and 73.7 % specificity. Furthermore, the peak time delay of less than 8.5 s was an independent predictor of robust collaterals and favourable clinical outcomes. CONCLUSIONS: Robust collateral status was significantly associated with the peak time delay in the ischemic core. It is a promising image marker for predicting collateral status and functional outcomes in AIS.

Plaque characteristics associated with failure of primary balloon angioplasty for intracranial atherosclerotic stenosis: a retrospective study.

BACKGROUND: Primary balloon angioplasty (PBA) is an alternative treatment approach for intracranial atherosclerotic stenosis (ICAS); however, its efficacy may be compromised by arterial dissection or early elastic recoil after balloon dilation. This study aimed to explore the association between plaque characteristics on high-resolution magnetic resonance vessel wall imaging (HR-VWI) and failure of PBA for ICAS. METHODS: We conducted a retrospective analysis of 113 patients with ICAS who underwent HR-VWI before endovascular treatment. Based on the presence of arterial dissection or early elastic recoil post-balloon dilation, patients were classified into the failed PBA (FPBA) group or the successful PBA (SPBA) group. Clinical and baseline HR-VWI characteristics were compared between the two groups. Multivariable analysis was used to investigate plaque features associated with the failure of PBA. RESULTS: The FPBA and SPBA groups comprised 74 and 39 patients, respectively. Plaque eccentricity (83.78% vs 46.15%, P<0.001), negative remodeling (90.54% vs 48.72%, P<0.001), remodeling index (median 0.73 vs 0.90, P=0.001), and intraplaque hemorrhage (31.08% vs 5.13%, P=0.002) differed significantly between the FPBA and SPBA groups. Multivariable analysis indicated that higher frequency of plaque eccentricity (OR 14.03, 95% CI 3.42 to 57.62, P<0.001) and negative remodeling (OR 6.11, 95% CI 1.22 to 30.71, P=0.028) were independently associated with failure of PBA. CONCLUSION: Our findings showed that failure of PBA was associated with plaque eccentricity and negative remodeling. Analysis of plaque characteristics on baseline HR-VWI holds potential value for identifying arterial dissection or early elastic recoil after angioplasty in patients with ICAS.

A Self-Adaptive Dual-ILRO Clock-Recovery Technique for Two-Tone Battery-Free Crystal-Free Neural-Recording SoC.

Wireless implantable devices are widely used in medical treatment, which should meet clinical constraints such as longevity, miniaturization, and reliable communication. Wireless power transfer (WPT) can eliminate the battery to reduce system size and prolong device life, while it's challenging to generate a reliable clock without a crystal. In this work, we propose a self-adaptive dual-injection-locked-ring-oscillator (dual-ILRO) clock-recovery technique based on two-tone WPT and integrate it into a battery-free neural-recording SoC. The 2[Formula: see text]-order inter-modulation (IM2) component of the two WPT tones is extracted as a low-frequency reference for battery-free SoC, and the proposed self-adaptive dual-ILRO technique extends the lock range to ensure an anti-interference PVT-robust clock generation. The neural-recording SoC includes a low-noise signal acquisition unit, a power management unit, and a backscatter circuit to perform neural signal recording, wireless power harvesting, and neural data transmission. Benefiting from the 6.4 µW low power of the clock recovery circuit, the overall SoC power is cut down to 49.8 µW. In addition, the proposed clock-recovery technique enables both signal acquisition and uplink communication to perform as well as that synchronized by an ideal clock, i.e., an effective number of 9.6 bits and a bit error rate (BER) less than 4.8 × 10-7 in chip measurement. The SoC takes a die area of 2.05 mm 2, and an animal test is conducted in a Sprague-Dawley rat to validate the wireless neural-recording performance, compared to a crystal-synchronized commercial chip.

SAD score of intracranial aneurysms for rupture risk assessment based on high-resolution vessel wall imaging.

OBJECTIVE: We aimed to develop a comprehensive model that integrates the radiological, morphological, and clinical factors to assess rupture risk for intracranial aneurysms. METHODS: We prospectively enrolled patients with intracranial saccular aneurysms who underwent high-resolution vessel wall imaging (HR-VWI) preoperatively. Clinical characteristics, aneurysm features and aneurysm wall enhancement scale (AWES) were recorded. AWES was categorized into three grades (no/faint/strong enhancement) by comparing AWE to enhancement of the pituitary infundibulum or choroid plexus on HR-VWI. Univariate and multivariate logistic regression analyses were performed to determine risk factors associated with aneurysmal rupture. RESULTS: A total of 25 ruptured and 116 unruptured aneurysms were included. Multivariate logistic regression analysis revealed that non-ICA site (OR 6.25, 95% CI 1.35-28.30, P = 0.019), AWES (OR 5.99, 95% CI 2.51-14.29, P < 0.001) and daughter sac or lobulated shape (OR 6.22, 95% CI 1.68-23.16, P = 0.006) were independent factors associated with ruptured aneurysms. The "SAD" model was generated and named after the first letters of each of these factors. SAD scores of 0-4 predicted 0, 2%, 12%, 42% and 100% ruptured aneurysms, respectively. The area under the receiver operating characteristic curve for the SAD model was 0.8822. CONCLUSION: The SAD model aids in distinguishing aneurysm rupture status and in managing unruptured aneurysms. Larger cohort studies are needed to confirm its applicability in predicting the rupture risk of unruptured aneurysms.

Evaluation of extent vs velocity of cortical venous filing in stroke outcome after endovascular thrombectomy.

PURPOSE: Abnormal venous drainage may affect the prognosis of patients undergoing endovascular reperfusion therapy (ERT). Herein, time-resolved dynamic computed tomography arteriography (dCTA) was applied to evaluate the relationship between the velocity and extent of cortical venous filling (CVF), collateral status and outcomes. METHODS: Thirty-five consecutive patients with acute anterior circulation occlusion who underwent ERT within 24 h of onset and successfully recanalized were enrolled. All patients underwent dCTA before ERT. Slow first or end of CVF was considered to occur when the time point of CVF appearance or disappearance on the affected side occurred after than that on the healthy side, whereas an equal CVF, a CVF reduced by ≤ 50%, or by > 50% on the affected side, were considered good, intermediate, and poor CVF extent, respectively. RESULTS: Slow first CVF (29 patients, 82.8%), slow end of CVF (29, 85.7%), and intermediate extent of CVF (7, 20.0%) were not associated with collateral status or outcomes. Poor extent of CVF (6, 17.1%) was associated with poor collateral status, higher proportion of midline shift, larger final infarct volume, higher modified Rankin Scale (mRS) score at discharge, and higher proportion of in-hospital mortality. All patients with transtentorial herniation had poor extent of CVF, and those with poor CVF extent had an mRS score ≥ 3 at discharge. CONCLUSION: Poor CVF extent, as assessed by dCTA, is a more accurate and specific marker than slow CVF to identify patients at high risk for poor outcomes after ERT.

A Wireless Headstage System Based on Neural-Recording Chip Featuring 315 nW Kickback-Reduction SAR ADC.

Wireless neural-recording instruments eliminate the bulky cables in multi-channel signal transmission, while the system size should be reduced to mitigate the impact on freely-moving animals. As the battery usually dominates the system size, the neural-recording chip should be low power to minimize the battery in long-termly monitoring. In general, a neural-recording chip consists of an analog front end (AFE) and an 8 bit -10 bit analog-to-digital converter (ADC), while it's challenging to design an ADC with an 8 -10 effective number of bits (ENOB) and sub- µ W power consumption due to the kickback noise. In this work, we propose a kickback-reduction technique for a successive-approximation-register (SAR) ADC based on neural-recording chip. Fabricated in 65 nm CMOS process, the proposed technique reduce the ADC power to 315 nW, resulting in an 8-channel neural-recording chip with 249 µW in total. Measured results show that the chip achieves an ADC ENOB of 9.73 bits, as well as an AFE gain of 43.3 dB and input-referred noise (IRN) of 9.68 µVrms in a bandwidth of 0.9 Hz -7.2 kHz. Combined with a BLE chip and a PCB antenna, the chip is implemented into a 2.6 g wireless headstage system (w/o battery), and an in-vivo demonstration is conducted on a male Sprague-Dawley rat with Parkinson's disease. The headstage system transfers the in-vivo neural signals to a commodity smartphone through BLE, and the miniature size induces little impact on freely-moving activities.

Control of Grain Shape and Size in Rice by Two Functional Alleles of OsPUB3 in Varied Genetic Background.

Grain shape and size are key determinants of grain appearance quality and yield in rice. In our previous study, a grain shape QTL, qGS1-35.2, was fine-mapped using near-isogenic lines (NILs) derived from a cross between Zhenshan 97 (ZS97) and Milyang 46 (MY46). One annotated gene, OsPUB3, was found to be the most likely candidate gene. Here, knockout and overexpression experiments were performed to investigate the effects of OsPUB3 on grain shape and size. Four traits were tested, including grain length, grain width, grain weight, and the ratio of grain length to width. Knockout of OsPUB3 in NILZS97, NILMY46, and another rice cultivar carrying the OsPUB3MY46 allele all caused decreases in grain width and weight and increases in the ratio of grain length to width. Results also showed that the magnitude of the mutational effects varied depending on the target allele and the genetic background. Moreover, it was found that NILZS97 and NILMY46 carried different functional alleles of OsPUB3, causing differences in grain shape rather than grain weight. In the overexpression experiment, significant differences between transgenic-positive and transgenic-negative plants were detected in all four traits. These results indicate that OsPUB3 regulates grain shape and size through a complex mechanism and is a good target for deciphering the regulatory network of grain shape. This gene could be used to improve grain appearance quality through molecular breeding as well.

A Power-Harvesting CGM Chiplet Featuring Silicon-Based Enzymatic Glucose Sensor.

Diabetes has become a leading cause of death and disability in the past decades. Continuous glucose monitoring (CGM) is a prevailing technique to determine the glucose level and provide in-time treatment. However, conventional CGM systems combine an electrochemical sensor with a CMOS chip, suffering from bulky size and interface issues. Integrating the CGM sensor on silicon is potential to miniaturize the CGM system and reduce the cost, while the recent silicon-based sensors show limited detection range and sensitivity. In this work, we present a silicon-based CGM chip let with wireless power transfer (WPT) and real-time wireless telemetry. Fabricated on a single silicon substrate, the chiplet consists of a silicon-based CGM sensor, a power-harvesting wireless-telemetry chip, and a silicon-based antenna. Measured results show that the chip let achieves a sensitivity of 4 µA.mM.cm-2 and a linear detection range of 0-10 mM. Based on WPT and backscattering communication, the chip let consumes 18.8 µ W power in glucose telemetry.

Remote cortical atrophy and language outcomes after chronic left subcortical stroke with aphasia.

Objective: Subcortical stroke can cause a variety of language deficits. However, the neural mechanisms underlying subcortical aphasia after stroke remain incompletely elucidated. We aimed to determine the effects of distant cortical structures on aphasia outcomes and examine the correlation of cortical thickness measures with connecting tracts integrity after chronic left subcortical stroke. Methods: Thirty-two patients and 30 healthy control subjects underwent MRI scanning and language assessment with the Western Aphasia Battery-Revised (WAB-R) subtests. Among patients, the cortical thickness in brain regions that related to language performance were assessed by the FreeSurfer software. Fiber tracts connecting the identified cortical regions to stroke lesions were reconstructed to determine its correlations with the cortical thickness measures across individual patient. Results: Cortical thickness in different parts of the left fronto-temporo-parietal (FTP) regions were positively related to auditory-verbal comprehension, spontaneous speech and naming/word finding abilities when controlling for key demographic variables and lesion size. Cortical thickness decline in the identified cortical regions was positively correlated with integrity loss of fiber tracts connected to stroke lesions. Additionally, no significant difference in cortical thickness was found across the left hemisphere between the subgroup of patients with hypoperfusion (HP) and those without HP at stroke onset. Conclusions: These findings suggest that remote cortical atrophy independently predicts language outcomes in patients with chronic left subcortical stroke and aphasia and that cortical thinning in these regions might relate to integrity loss of fiber tracts connected to stroke lesions.

Neural Dielet: A 0.4mm 3 Battery-Less Crystal-Less Neural-Recording System on Die Achieving 1.6cm Backscatter Range with 2mm×2mm On-Chip Antenna.

Miniaturization is essential in the design of wireless neural-recording systems. In recent years, the battery in neural-recording systems can be eliminated by wireless power transfer (WPT), while antenna and crystal become two main bottlenecks to minimize a battery-less neural implant. In conventional battery-less designs, the miniaturization of antenna led to a short communication range, and a crystal-less clock suffered from noise issue or power-hungry circuits. In this work, we demonstrate a 0.4mm 3 neural dielet, which is a battery-less crystal-less neural-recording system on die (SoD) within a 2mm×2mm on-chip coil antenna. The communication range through the ultra-small antenna is extended by a proposed dither-based 3 rd-order intermodulation (IM3) technique, which prevents the backscatter communication from WPT blocker. Meanwhile, a dither-based 2 nd-order intermodulation (IM2) wireless-lock technique is proposed to remove the crystal. Measured results show that the SoD consumes 53.2 µ W power and achieves a wireless communication range of 1.6cm at a bit-error rate (BER) of 8 ×10-6, accompanied by simultaneous WPT for battery-less operation. In the animal experiment, the neural signal wirelessly recorded by our SoD in a battery-less way matches favorably with the wire-test results obtained by a commercial chip.

Poor Internal Jugular Venous Outflow Is Associated with Poor Cortical Venous Outflow and Outcomes after Successful Endovascular Reperfusion Therapy.

Many patients show poor outcomes following endovascular reperfusion therapy (ERT), and poor cortical venous outflow is a risk factor for these poor outcomes. We investigated the association between the outflow of the internal jugular vein (IJV) and baseline cortical venous outflow and the outcomes after ERT. We retrospectively enrolled 78 patients diagnosed with an acute anterior circulation stroke and successful ERT. Poor IJV outflow on the affected side was defined as stenosis ≥50% or occlusion of ipsilateral IJV, and poor outflow of bilateral IJVs was defined as stenosis ≥50% or occlusion of both IJVs. Poor cortical venous outflow was defined as a cortical vein opacification score (COVES) of 0 on admission. Multivariate analysis showed that poor outflow of IJV on the affected side was an independent predictor for hemorrhagic transformation. The poor outflow of bilateral IJVs was an independent risk factor for poor clinical outcomes. These patients also had numerical trends of a higher incidence of symptomatic intracranial hemorrhage, midline shift >10 mm, and in-hospital mortality; however, statistical significance was not observed. Additionally, poor IJV outflow was an independent determinant of poor cortical venous outflow. For acute large vessel occlusion patients, poor IJV outflow is associated with poor baseline cortical venous outflow and outcomes after successful ERT.

Comparative analysis of the diffusion kurtosis imaging and diffusion tensor imaging in grading gliomas, predicting tumour cell proliferation and IDH-1 gene mutation status.

INTRODUCTION: Few studies have applied diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) for the comprehensive assessment of gliomas [tumour grade, isocitrate dehydrogenase-1 (IDH-1) mutation status and tumour proliferation rate (Ki-67)]. This study describes the efficacy of DKI and DTI to comprehensively evaluate gliomas, compares their results. METHODS: Fifty-two patients (18 females; median age, 47.5 years) with pathologically proved gliomas were prospectively included. All cases underwent DKI examination. DKI (mean kurtosis: MK, axial kurtosis: Ka, radial kurtosis: Kr) and DTI (mean diffusivity: MD, fractional anisotropy: FA) maps of each metric was derived. Three ROIs were manually drawn. RESULTS: MK, Ka, Kr and FA were significantly higher in HGGs than in LGGs, whereas MD was significantly lower in HGGs than in LGGs (P < 0.01). ROC analysis demonstrated that MK (specificity: 100% sensitivity: 79%) and Ka (specificity: 96% sensitivity: 82%) had the same and highest (AUC: 0.93) diagnostic value. Moreover, MK, Ka, and Kr were significantly higher in grade III than II gliomas (P ≦ 0.01). Further, DKI and DTI can significantly identify IDH-1 mutation status (P ≦ 0.03). Ka (sensitivity: 74%, specificity: 75%, AUC: 0.72) showed the highest diagnostic value. In addition, DKI metrics and MD showed significant correlations with Ki-67 (P ≦ 0.01) and Ka had the highest correlation coefficient (rs = 0.72). CONCLUSIONS: Compared with DTI, DKI has great advantages for the comprehensive assessment of gliomas. Ka might serve as a promising imaging index in predicting glioma grading, tumour cell proliferation rate and IDH-1 gene mutation status.

Quantitative analysis of neurite orientation dispersion and density imaging in grading gliomas and detecting IDH-1 gene mutation status.

Background and purpose: Neurite orientation dispersion and density imaging (NODDI) is a new diffusion MRI technique that has rarely been applied for glioma grading. The purpose of this study was to quantitatively evaluate the diagnostic efficiency of NODDI in tumour parenchyma (TP) and peritumoural area (PT) for grading gliomas and detecting isocitrate dehydrogenase-1 (IDH-1) mutation status. Methods: Forty-two patients (male: 23, female: 19, mean age: 44.5 y) were recruited and underwent whole brain NODDI examination. Intracellular volume fraction (icvf) and orientation dispersion index (ODI) maps were derived. Three ROIs were manually placed on TP and PT regions for each case. The corresponding average values of icvf and ODI were calculated, and their diagnostic efficiency was assessed. Results: Tumours with high icvfTP (≥0.306) and low icvfPT (≤0.331) were more likely to be high-grade gliomas (HGGs), while lesions with low icvfTP (<0.306) and high icvfPT (>0.331) were prone to be low-grade gliomas (LGGs) (P < 0.001). A multivariate logistic regression model including patient age and icvf values in TP and PT regions most accurately predicted glioma grade (AUC = 0.92, P < 0.001), with a sensitivity and specificity of 92% and 89%, respectively. However, no significant differences were found in NODDI metrics for differentiating IDH-1 mutation status. Conclusions: The quantitative NODDI metrics in the TP and PT regions are highly valuable for glioma grading. A multivariate logistic regression model using the patient age and the icvf values in TP and PT regions showed very high predictive power. However, the utility of NODDI metrics for detecting IDH-1 mutation status has not been fully explored, as a larger sample size may be necessary to uncover benefits.

Cortical vein thrombosis in adult patients of cerebral venous sinus thrombosis correlates with poor outcome and brain lesions: a retrospective study.

BACKGROUND: Cortical vein thrombosis (CVT) receives little attention in adult patients with cerebral venous sinus thrombosis (CVST). This study aimed to investigate the clinical and radiological features of adult CVST patients with concomitant CVT. METHODS: From May 2009 to May 2016, we recruited 44 adult CVST patients (diagnosed within 1 month of onset; 33.8 ± 14.0 years of age, 28 males). CVT was primarily confirmed using computed tomography venography and magnetic resonance imaging sequence of contrast enhanced three dimensions magnetization prepared rapid acquisition with gradient echo. Patients with concomitant CVT were divided into the CVT group; otherwise, the patients were placed into the non-CVT group. The clinico-radiological characteristics were compared between the two groups. RESULTS: The CVT group included 27 patients (61.4%), and the non-CVT group included 17 patients (38.6%). Seizure (63.0% versus 11.8%), focal neurological deficits (44.4% versus 5.9%), and consciousness disorders (33.3% versus 0) occurred more frequently in the patients in the CVT group than in those of the non-CVT group (P < 0.05). The modified Rankin Scale (mRS) score at discharge was higher for the CVT group patients (median 2, range 1-4) than for the non-CVT group patients (median 0, range 0-4) (P < 0.001). Venous infarction (63.0% versus 11.8%), parenchymal hemorrhage (40.7% versus 5.9%), and subarachnoid hemorrhage (22.2% versus 0) were identified more frequently in the CVT group than in the non-CVT group (P < 0.05). CONCLUSIONS: This study demonstrates that concomitant CVT is a common finding in adult patients with CVST and is associated with severe clinical manifestations, poor short-term outcomes, and brain lesions.

Relationship between visible branch arteries distal to the stenosis on magnetic resonance angiography and stroke recurrence in patients with severe middle cerebral artery trunk stenosis: a one-year follow up study.

BACKGROUND: To evaluate the relationship between the flow signal intensity of branch arteries distal to the stenosis on 3-dimensional (3D) time-of-flight (TOF) magnetic resonance angiography (MRA) and the risk of stroke recurrence in patients with severe middle cerebral artery (MCA) trunk stenosis. METHODS: We prospectively recruited 153 patients (mean age 62.9 ± 13.0 years, 106 males) with a first ischemic stroke or transient ischemic attack caused by a severe MCA trunk stenosis (70 % to 99 %) confirmed by 3D TOF MRA and followed them for one year to determine the stroke recurrence. The MCA branch signal intensity distal to the site of stenosis on 3D TOF MRA was classified as either good (grade A) or poor [mild reduction (grade B) or severe reduction (grade C)] according to the extent to which the MCA could be visualized. The patients were divided into groups A (35), B (58), or C (60) based on the MRA grading of the MCA branch signal intensity distal to the site of stenosis. RESULTS: Poor MCA branch signal intensity was associated with internal border-zone infarction (p < 0.05). The risk of stroke recurrence in the ipsilateral MCA in the first year was 18.3 %. The 1-year cumulative incidence of recurrence was higher in the patients in group C (30 %) than in groups B (12.1 %) or A (8.6 %) (Log rank, p = 0.007). Multivariate analyses via Cox proportional hazard regression demonstrated that only a grade C classification of the signal intensity of the MCA branches was an independent predictor of stroke recurrence in the ipsilateral MCA (hazard ratio = 3.0, 95 % confidence interval = 1.3-7.4, p = 0.014). CONCLUSIONS: This study demonstrated that MCA branch signal intensity as assessed via 3D TOF MRA may be a useful and simple tool to stratify the risk of stroke recurrence in patients with severe MCA trunk stenosis.