Intraneural Blood Flow Research Articles

Nerve sonography to detect intraneural microvascularity in patients with peripheral neuropathy

ObjectiveWe assessed microvessel flow within peripheral nerves using nerve sonography in patients with peripheral neuropathy. MethodsThis study included consecutive patients with peripheral neuropathy who were admitted to our hospital. The patients were divided into two groups: inflammatory neuropathies for immune-mediated neuropathies, such as Guillain − Barré syndrome and chronic inflammatory demyelinating polyneuropathy, and the rest were defined as non-inflammatory neuropathies. We assessed nerve size and intraneural blood flow at four sites on each median and ulnar nerve. Blood flow was evaluated using color Doppler imaging, advanced dynamic flow (ADF), and superb microvascular imaging (SMI) techniques. ResultsThirty-nine patients (median age, 60.0 years; 20 male) were enrolled in this study. An increase in intraneural blood flow was observed in five patients when evaluated by color Doppler, five patients by ADF, and 13 patients by SMI. An overall analysis of the three methods showed that intraneural blood flow was significantly higher in patients with inflammatory neuropathy than in those with non-inflammatory neuropathy (54.2% vs. 0%, p = 0.0005). ConclusionsIntraneural hypervascularization is more frequent in patients with inflammatory neuropathy than in those with non-inflammatory neuropathy. SignificanceEvaluation of microvessel flow within peripheral nerves may contribute to the diagnosis of peripheral neuropathy.

Doppler Sonography Evaluation of Median Nerve Intraneural Blood Flow: A Systematic Review

Objective: This systematic review aims to determine the extent, scope, and nature of research using the sonographic measurement of intraneural blood flow within the median nerve and to identify, characterize, and compare image acquisition and analysis protocols that have been reported as potential candidate techniques for standardizing research and clinical applications. Materials and Methods: This systematic review summarizes image acquisition protocols and analysis methodologies from 52 current research studies using Doppler ultrasound to examine median nerve intraneural blood flow. Results: Four types of Doppler technologies were identified: power Doppler, color Doppler, spectral Doppler, and Superb Microvascular Imaging, but there were inconsistencies in how images were acquired and analyzed. Intraneural blood flow measurements were categorized into four types based on a combination of measurement level (e.g., binary, ordinal, continuous) and type of flow indicator (e.g., pixel count, intensity, velocity). Conclusion: Standardized imaging protocols and reporting guidelines are needed to improve consistency. Future studies should evaluate the accuracy and reliability of different image acquisition methods and analysis measurements.

Assessing the Potential for Error in Investigating Intraneural Vascularity: A Need for a Standardized Imaging Protocol.

This study examined the implementation of a Doppler sonography imaging protocol to assess intraneural blood flow, within the median nerve, in healthy individuals. A total of 176 participants were examined, and this involved 717 retrospective observations of the images collected. The implemented imaging protocol was assessed, and the data that were collected were cleaned and checked for fidelity and validity. A large percentage of missing evidence (11%-35%) across proximal, mid, and distal carpal tunnel locations. Only a quarter of cases with evidence of intraneural blood flow had the strongest evidence of a power Doppler video clip, of which only three-quarters were valid. The study identified potential areas for improving the imaging protocol to reduce missing data and improve data quality. This study demonstrates the significance of a standardized imaging protocol to guide the sonographic acquisition of Doppler images and provides important insights into potential issues with data quality. The recommendations have the potential to help future studies assess intraneural blood flow in healthy populations in a more rigorous and reliable way. Incorporating the study's recommendations into a standardized protocol, there is potential to enhance the diagnostic accuracy of carpal tunnel syndrome and improve diagnosis and treatment.

Visual Evoked Potentials for the Detection of Diabetic Retinal Neuropathy.

Visual evoked potentials (VEP) are visually evoked signals that extract electroencephalographic activity in the visual cortex that can detect retinal ganglion cells, optic nerves, chiasmal and retrochiasmal dysfunction, including optic radiations, and the occipital cortex. Because diabetes causes diabetic retinopathy due to microangiopathy and neuropathy due to metabolic abnormalities and intraneural blood flow disorders, assessment of diabetic visual pathway impairment using VEP has been attempted. In this review, evidence on the attempts to assess the visual pathway dysfunction due to abnormal blood glucose levels using VEP is presented. Previous studies have provided significant evidence that VEP can functionally detect antecedent neuropathy before fundus examination. The detailed correlations between VEP waveforms and disease duration, HbA1c, glycemic control, and short-term increases and decreases in blood glucose levels are evaluated. VEP may be useful for predicting postoperative prognosis and evaluating visual function before surgery for diabetic retinopathy. Further controlled studies with larger cohorts are needed to establish a more detailed relationship between diabetes mellitus and VEP.

Evaluation of Sciatic Nerve Stiffness Using Shear Wave Elastography in Patients with Unilateral Diabetic Foot Ulcers.

To evaluate the stiffness of the sciatic nerve by shear wave elastography (SWE) and to determine whether SWE can be used to predict diabetic foot ulcer (DFU) in a patient with diabetic peripheral neuropathy (DPN). Sixteen patients (thirty-two lower limbs) with unilateral DFU were studied retrospectively. The ultrasonographic parameters including cross-sectional area (CSA) of sciatic nerve, intraneural blood flow, peak systolic velocity (Vmax) and resistive index (RI) in the intraneural artery of the sciatic nerve, and the SWE stiffness value of the sciatic nerve were measured. The examinations of arteries of the lower limbs were also performed by ultrasound. According to the presence or absence of DFU, the 32 lower limbs were divided into two groups: the DFU group and the non-DFU group. The ultrasonographic parameters were compared between these two groups. There was no significant difference (p > 0.05) between the two groups for CSA, intraneural blood flow, Vmax and RI in the intraneural artery of the sciatic nerve, and numbers of severe artery stenosis or full occlusion of the artery in the lower limbs. However, SWE stiffness values in the sciatic nerve in the DFU group are higher than the non-DFU group (p < 0.05). When the SWE stiffness values were used for prediction of DFU in patients with DPN, the area under the ROC curve (AUC) was 0.727 (95% CI: 0.541-0.868). When the best SWE stiffness value of 24.48 kPa was taken as a cutoff for prediction of DFU, the sensitivity was 62.50% (95% CI: 35.4-84.8%), and the specificity was 75% (95% CI: 47.6-92.7%). Sciatic nerve stiffness is significantly higher in lower limbs with DFU. SWE is a noninvasive imaging method that may be used to evaluate sciatic nerve stiffness, then potentially predict DFU in patients with DPN.

Thirty Minutes of Sub-diastolic Blood Flow Occlusion Alters Carpal Tunnel Tissue Function and Mechanics.

There is evidence that carpal tunnel syndrome (CTS) development is driven by vascular factors, specifically those resulting from ischemia and edema. The purpose of this study was to investigate the vascular hypothesis of CTS development by quantifying the temporal effects of 30 min of sub-diastolic brachial blood flow occlusion on median nerve edema, intraneural blood flow velocity, nerve function as measured through nerve conduction study (NCS), tendon-connective tissue mechanics and carpal tunnel tissue stiffness. Forty healthy volunteers underwent 30 min of sub-diastolic brachial occlusion while an NCS and ultrasound examination were performed consecutively every 5 min. Motor latency (p < 0.001), sensory conduction velocity (p < 0.001), sensory amplitude (p=0.04), nerve blood flow (p < 0.001), peak relative flexor digitorum superficialis tendon-sub-synovial connective tissue displacement (p=0.02) and shear strain (p=0.04) were significantly affected by partial ischemia. Our results highlight the dependency of carpal tunnel tissue function on adequate blood flow.

Peripheral nerve morphology and intraneural blood flow in chronic kidney disease with and without diabetes.

Introduction/AimsSonographic alterations of peripheral nerves in pre‐dialytic kidney disease are yet to be determined. We aimed to assess peripheral nerve cross‐sectional area (CSA) and intraneural blood flow in patients with pre‐dialytic chronic kidney disease (CKD) and diabetic kidney disease (DKD).MethodsSubjects with CKD (n = 20) or DKD (n = 20) underwent ultrasound to assess CSA of the median and tibial nerves as well as intraneural blood flow of the median nerve. Blood flow was quantified using maximum perfusion intensity. Neuropathy was assessed using the Total Neuropathy Score. A 6‐m timed walk test was also performed. Healthy controls (n = 28) were recruited for comparison.ResultsThe DKD group had more severe neuropathy (p = .024), larger tibial nerve CSA (p = .002) and greater median nerve blood flow than the CKD group (p = .023). Blood flow correlated with serum potassium in disease groups (r = 0.652, p = .022). Disease groups had larger tibial nerve CSA than controls (p < .05). No blood flow was detected in controls. Tibial nerve enlargement was associated with slower maximal walking speeds in disease groups (r = −0.389, p = .021).DiscussionSubjects with DKD demonstrated enlarged tibial nerve CSA and increased median nerve blood flow compared to those with CKD. Elevations in serum potassium were associated with increased blood flow. Sonographic alterations were detectable in pre‐dialytic kidney disease compared to controls, highlighting the utility of ultrasound in the assessment of nerve pathology in these patient groups.

Angiosomes of the Ulnar Nerve at the Elbow: A Cadaver Trial Using Contrast-Enhanced Ultrasound.

Three major arteries supplying the ulnar nerve in the cubital tunnel are commonly known. However, their vascular territories (angiosomes) have not been described yet. Contrast-enhanced ultrasound was used to identify the angiosomes of posterior ulnar recurrent artery, inferior ulnar collateral artery and superior ulnar collateral artery in 20 fresh, non-frozen human body donors. The arteries were cannulated, and physiologic blood flow was simulated. Contrast agent was applied in each vessel in a randomized sequence, and the length of the contrast-enhancing ulnar nerve segment was measured by a radiologist blinded to the sequence. The angiosome of the posterior ulnar recurrent artery overlaps both other angiosomes. It fully covers the cubital tunnel in 63.6% of specimens. In addition, collateral flow via nerve and muscle branches of the arterial anastomotic network around the elbow (rete articulare cubiti) partly maintains the intra-neural blood flow in the absence of a vascular pedicle. The posterior ulnar recurrent artery is the dominant nutrient vessel of the ulnar nerve in the cubital tunnel. A potential watershed zone exists proximal to the Osborne ligament. Knowledge of these angiosomes may advance surgery of the ulnar nerve in the cubital tunnel.

Influence of temperature on sonographic images of the median nerve for the diagnosis of carpal tunnel syndrome: a case control study

BackgroundIn addition to nerve conduction studies (NCSs), ultrasonography has been widely used as an alternative tool for diagnosing carpal tunnel syndrome (CTS). Although the results of NCSs are influenced by local skin temperature, few studies have explored the effects of skin temperature on ultrasonography of the median nerve. Since swelling and intraneural blood flow of the median nerve might be influenced by local temperature changes, the aim of this study was to evaluate the cross-sectional area (CSA) and intraneural blood flow of the median nerve under three skin temperatures (30 °C, 32 °C, 34 °C).MethodsFifty patients with CTS and 50 healthy volunteers were consecutively recruited from a community hospital. Each participant received physical examinations and NCSs and underwent ultrasonography, including power Doppler, to evaluate intraneural vascularity.ResultsThe CSA of the median nerve in the CTS patients was significantly larger than that in the healthy controls at all three temperatures. However, significant differences in the power Doppler signals of the median nerve between the two studied groups were observed only at 30 and 32 °C, not at 34 °C.ConclusionThe significant difference in the intraneural vascularity of the median nerve between the patients with CTS and the healthy subjects was lost at higher temperatures (34 °C). Therefore, the results of power Doppler ultrasonography in diagnosing CTS should be cautiously interpreted in patients with a high skin temperature or those who reside in warm environments.

Dynamic Evaluation of Intraneural Microvascularity of the Ulnar Nerve Using Contrast-Enhanced Ultrasonography in Patients With Cubital Tunnel Syndrome

The purpose of this study was to compare the intraneural microvascular patterns of the ulnar nerve at 2 elbow flexion angles in asymptomatic volunteers and patients with cubital tunnel syndrome (CuTS) and to evaluate the effects of surgery on the microvascular pattern in patients with CuTS by using contrast-enhanced ultrasonography (CEUS). This study included 10 elbows in 10 asymptomatic volunteers (control group) and 10 elbows in 10 patients with CuTS who underwent anterior subcutaneous transposition of the ulnar nerve (CuTS group). The CuTS group underwent clinical and electrophysiologic examinations and CEUS before surgery and at 1, 2, and 3 months after surgery. The intraneural enhancement pattern was calculated as an area under the curve (AUC) value in the entrapment site of the ulnar nerve within the cubital tunnel and in the area 1 cm proximal to the site (proximal site) at elbow flexion angles of 20° and 110°. Serial electrophysiologic examinations showed improvements at 1, 2, and 3 months after surgery compared with before surgery. In the control group, the AUC values of the central part of the cubital tunnel and proximal sites showed no substantial changes with the increase in elbow flexion. In the CuTS group, the AUC in the proximal site at 110° of elbow flexion was decreased compared with that at 20° of flexion before surgery. The AUC values for both the entrapment and proximal sites at 20° and 110° of elbow flexion were the most increased at 2 months after surgery compared with before surgery. Increased elbow flexion in patients with CuTS influences the intraneural blood flow of the ulnar nerve. Surgery for CuTS alters the intraneural blood flow. Quantitative evaluation of the intraneural blood flow of the ulnar nerve using CEUS may be a new supplementary diagnostic tool for CuTS and an indicator for the evaluation of postoperative recovery from nerve damage.

Intraoperative infrared fluorescence angiography in surgery of peripheral nerve injuries

Often, when performing reconstruction of nerve trunks, between the ends of the damaged nerve, the presence of diastasis is noted, which requires significant nerve tension in order to overcome it. This, in turn, can lead to a violation of the blood supply to the nerve and damage to its ultrastructures, which leads to unsatisfactory treatment results. The possibility of using intraoperative infrared fluorescence angiography in reconstructive surgical interventions for peripheral nerve damage, in order to assess the degree of blood flow disturbance in the nerve trunk, is considered. In patients with a complete anatomical break during the operation, an attempt was made to overcome diastasis by measuring the tension force (up to 3 N) with which the nerve was affected. Infrared fluorescence angiography with indocyanine green was performed simultaneously. The obtained angiograms were analyzed, and the effect of the tension force on the change in blood flow in the nerve trunk was determined. It was found that when exposed to a force of up to 2 N, there is no significant change in the intraneural blood flow. At the same time, the effect of a force of 3 N is manifested on angiograms by a significant decrease in the volume of blood flow, which is usually due to constriction of the vessels due to their stretching. After reconstruction (microsurgical epineural suture), repeated angiography was performed to assess the safety and adequacy of blood supply to the nerve. It was revealed that the use of intraopreational angiography with indocyanin green is an affordable and easily feasible technique that allows to determine the safety and, equally important, the adequacy and efficiency of blood flow in the nerve trunk. This technique makes it possible to monitor the safety of blood flow in the nerve trunk, to study the mechanisms of compensation of blood supply to the nerve after microsurgical epineural suture, to assess the quality of comparison of nerve stumps along the axis, excluding the possibility of their "twist".

Ultrasound examination predicts 6-month progression in carpal tunnel syndrome patients.

Carpal tunnel syndrome (CTS) is a peripheral neuropathy resulting from chronic median nerve compression. Chronic compression leads to neurological changes that are quantified through nerve conduction studies (NCS). Although NCS represents the gold standard in CTS assessment, they provide limited prognostic value. Several studies have identified ultrasound as a tool in diagnosing and potentially predicting the progression of CTS in patients. The purpose of this study was to evaluate the predictive value of ultrasound examination in CTS patients. Twenty patients recruited at their first visit with the neurologist completed two NCS and ultrasound examinations approximately 6 months apart. Ultrasound examination consisted of B-mode, pulse-wave Doppler and colour Doppler ultrasound videos and images to quantify median nerve cross-sectional area, intraneural blood flow velocity in three wrist postures (15° flexion, neutral, and 30° extension), and displacement of the flexor digitorum superficialis (FDS) tendon and the adjacent subsynovial connective tissue (SSCT) of the middle finger during repetitive finger flexion-extension cycles. A questionnaire was administered to assess the work-relatedness of CTS. Linear regression analyses revealed that intraneural blood flow velocity (R2 = 0.36, p = .03), assessed in wrist flexion, and relative FDS-SSCT displacement (R2 = 0.27, p = .04) and shear strain index (R2 = 0.28, p = .04) were significant predictors of nerve sensory and motor changes at 6 months. Results suggest the possibility of using a battery of ultrasound measures as viable markers to predict median nerve functional changes within 6 months.

Effect of Force, Posture, and Repetitive Wrist Motion on Intraneural Blood Flow in the Median Nerve.

Pinching, deviated wrist postures, and repetitive motion are risk factors for carpal tunnel syndrome. Hypervascularization of the median nerve and increased intraneural blood flow proximal to the carpal tunnel result in finger force and deviated wrist postures. The purpose of this study was to determine the effects of pinching with and without force, wrist posture, and repetitive wrist motion on intraneural blood flow in the median nerve. Eleven healthy and 11 carpal tunnel syndrome-symptomatic individuals completed 3 sections of this study: 15 pinch posture force trials, 3 repetitive wrist motion trials, and 3 static wrist posture trials. Intraneural blood flow (centimeters per second) was measured with pulsed wave Doppler ultrasound during each trial. Transverse B-mode images obtained from static trials were used to calculate the median nerve cross-sectional area and circumference. An analysis of variance statistical analysis revealed significant main effects of pinch posture force (F4,80 = 21.397; P < .001) and wrist posture (F2,40 = 14.545; P < .001). Intraneural blood flow velocities were significantly greater when 6 N of force was applied by the thumb, finger, or pinch compared to no applied force in the same postures. Intraneural blood flow velocities were higher at 30° wrist flexion (mean ± SD, 2.24 ± 0.42 cm/s) than neutral (2.06 ± 0.45 cm/s) and 30° wrist extension (1.97 ± 0.46 cm/s). No changes were found in response to repetitive wrist motion. Flexed wrists as well as applied finger and thumb forces increase median nerve blood flow at the entry to the carpal tunnel, which may negatively affect the median nerve.

ドプラ法超音波での手根管開放術後の正中神経Intraneural Blood Flow所見の変化

ドプラ法超音波での手根管開放術後の正中神経Intraneural Blood Flow所見の変化

Blood flow velocity but not tendon mechanics relates to nerve function in carpal tunnel syndrome patients

Carpal tunnel syndrome (CTS) develops from chronic compression of the median nerve. Chronic compression results in a number of vascular, structural and functional changes to the carpal tunnel tissues which ultimately manifest in the characteristic symptoms of CTS. The purpose of this study was to investigate the interplay of median nerve function, median nerve hemodynamics, and finger flexor tendon and subsynovial connective tissue (SSCT) mechanics in CTS patients. Thirty-five patients were recruited following nerve conduction study for this double-blinded imaging study. Ultrasound B-mode, pulse-wave Doppler, and colour Doppler images and videos were collected at the proximal carpal tunnel to quantify: (1) median nerve cross-sectional area, (2) intraneural blood flow velocity in 3 wrist postures (neutral (0°), flexion (15°), extension (30°)), and (3) flexor digitorum superficialis and SSCT displacement. Results demonstrate that intraneural blood flow velocity is dependent on median nerve function and wrist posture such that patients with mild CTS are more susceptible to the effects of non-neutral wrist postures. Tendon-SSCT mechanics do not appear to differ based on severity. This study stresses the importance of limiting exposure to non-neutral wrist postures in patients with early signs of the condition.

Doppler sonography for intraneural vascularization of ulnar neuropathy at the elbow – Before and after surgery

The finding of intraneural blood flow (IBF) signal by doppler sonography was interpreted in several ways at entrapment neuropathy. There is no report of IBF after surgery of ulnar neuropathy at the elbow (UNE). We investigated IBF in UNE before and after surgery. Case series study. Subject: nine arms (only men) diagnosed and confirmed as UNE by surgery. All arms were performed grey scale sonography (GS) using an ultrasound machine (AprioXV; Toshiba) with 12 MHz linear-array transducer and electrodiagnostic study (EDX) before and after surgery. We performed Doppler sonography (DS): 5 arms before surgery, 6 arms after surgery and 2 arms both. In EDX, diagnosis of UNE as follows: absolute motor CV from above elbow to below elbow of less than 50 m/s and (1) or (2) (1) differential slowing (10 m/s across elbow). (2) conduction block across elbow. In GS, diagnosis of UNE as follows: cut-off value was the largest cross-sectional area from 2 cm distal to 2 cm proximal to the medial epicondyle > 11 mm 2 . General findings before surgery: EDX diagnosed 8 arms as UNE but one. Seven arms were diagnosed as UNE by GS. General findings after surgery: All 9 arms were improved in clinical signs. EDX did not change. Eight were diagnosed as UNE by GS. DS findings before surgery: IBF signal was not detected in 3 arms and detected in 2 arms but absent pulse. DS findings of after surgery: six arms were detected IBF signal and pulsatility. These findings may suggest that releasing entrapment site might decrease endoneurial fluid pressure and increase IBF. About recovery from UNE after surgery, it may be useful to evaluate intraneural vascularity at the affected site with DS.

Superb Microvascular Imaging of the Median Nerve in Carpal Tunnel Syndrome: An Electrodiagnostic and Ultrasonographic Study.

To evaluate intraneural blood flow of the median nerve using superb microvascular imaging (SMI) and power Doppler ultrasonography (PDUS), and to examine their correlation with electroneuromyography in patients with carpal tunnel syndrome (CTS). A cross-sectional survey was used, and the study was conducted in the research unit of a training and research hospital. Patients diagnosed with CTS according to electroneuromyography studies were included in the study. Ultrasound measurements were taken using an Aplio-500 (Toshiba Medical System Corporation, Tokyo, Japan) device and a linear multifrequency 14-MHz probe. The cross-sectional area of the median nerve at the carpal tunnel level was measured by the direct tracing method using electronic calipers. The power Doppler ultrasonography and superb microvascular imaging scores were recorded by grading the vascularity between 0 and 3. Evaluation was made of a total of 113 hands of 80 patients (18 men, 62 women) with a mean age of 34.67 ± 12.82 years. The mean duration of symptoms was 12.34 ± 6.66 months. When the patients were grouped as mild, moderate, and severe CTS, there was a statistically significant difference between the SMI and PDUS grades (P < .05). As the severity of CTS increased, an increase in SMI and PDUS scores was observed. There was a strong correlation between SMI scores and motor distal latency (r = .71/P = .026), amplitude of sensory action potential (r = -.77/P = .029), and sensory neurotransmission rate (r = .77/P = .029). SMI seems to be more sensitive than PDUS for evaluating the vascularity of the median nerve in patients with CTS, and SMI grading is correlated with the ENMG results.

Ultrasonographic demonstration of intraneural neovascularization after penetrating nerve injury.

Hypervascularization of nerves has been shown to be a pathological sign in some peripheral nerve disorders, but has not been investigated in nerve trauma. An observational cohort study was performed of the intraneural blood flow of 30 patients (34 nerves) with penetrating nerve injuries, before or after nerve reconstruction. All patients underwent electrophysiological assessment, and B-mode and color Doppler ultrasonography. Intraneural hypervascularization proximal to the site of injury was found in all nerves, which was typically marked and had a longitudinal extension of several centimeters. In 6 nerves, some blood flow was also present within the injury site or immediately distal to the injury. No correlation was found between the degree of vascularization and age, size of the scar / neuroma, or degree of reinnervation. Neovascularization of nerves proximal to injury sites appears to be an essential element of nerve regeneration after penetrating nerve injuries. Muscle Nerve 57: 994-999, 2018.

Effects of hemodialysis on intraneural blood flow in end-stage kidney disease.

We quantified intraneural blood flow (INBF) in 18 patients with end-stage kidney disease (ESKD) and examined its relationship with nerve size, neuropathy severity, and nerve excitability parameters. Sonographic measurements of the median nerve were performed at the same site before and after hemodialysis. INBF was quantified by analyzing power Doppler sonograms to obtain the vessel score (VSc) and maximum perfusion intensity (MPI). Corresponding median motor nerve excitability studies were performed. Neuropathy severity was assessed using Total Neuropathy Score. A total of 39% of ESKD patients had detectable INBF compared with none in the control group (P < 0.0001). Patients with detectable INBF had larger nerves and more severe neuropathy (P < 0.01). INBF parameters were significantly reduced after a session of dialysis (VSc: P < 0.01; MPI: P < 0.01). A significant relationship was found between interdialytic change in INBF and changes in nerve excitability. Increased INBF is a potential marker for neuropathy severity in ESKD patients. Muscle Nerve 57: 287-293, 2018.

The design of and chronic tissue response to a composite nerve electrode with patterned stiffness

Objective. As neural interfaces demonstrate success in chronic applications, a novel class of reshaping electrodes with patterned regions of stiffness will enable application to a widening range of anatomical locations. Patterning stiff regions and flexible regions of the electrode enables nerve reshaping while accommodating anatomical constraints of various implant locations ranging from peripheral nerves to spinal and autonomic plexi. Approach. Introduced is a new composite electrode enabling patterning of regions of various electrode mechanical properties. The initial demonstration of the composite’s capability is the composite flat interface nerve electrode (C-FINE). The C-FINE is constructed from a sandwich of patterned PEEK within layers of pliable silicone. The shape of the PEEK provides a desired pattern of stiffness: stiff across the width of the nerve to reshape the nerve, but flexible along its length to allow for bending with the nerve. This is particularly important in anatomical locations near joints or organs, and in constrained compartments. We tested pressure and volume design constraints in vitro to verify that the C-FINE can attain a safe cuff-to-nerve ratio (CNR) without impeding intraneural blood flow. We measured nerve function as well as nerve and axonal morphology following 3 month implantation of the C-FINE without wires on feline peripheral nerves in anatomically constrained areas near mobile joints and major blood vessels in both the hind and fore limbs. Main Results. In vitro inflation tests showed effective CNRs (1.93 ± 0.06) that exceeded the industry safety standard of 1.5 at an internal pressure of 20 mmHg. This is less than the 30 mmHg shown to induce loss of conduction or compromise blood flow. Implanted cats showed no changes in physiology or electrophysiology. Behavioral signs were normal suggesting healthy nerves. Motor nerve conduction velocity and compound motor action potential did not change significantly between implant and explant (p > 0.15 for all measures). Axonal density and myelin sheath thickness was not significantly different within the electrode compared to sections greater than 2 cm proximal to implanted cuffs (p > 0.14 for all measures). Significance. We present the design and verification of a novel nerve cuff electrode, the C-FINE. Laminar manufacturing processes allow C-FINE stiffness to be configured for specific applications. Here, the central region in the configuration tested is stiff to reshape or conform to the target nerve, while edges are highly flexible to bend along its length. The C-FINE occupies less volume than other NCEs, making it suitable for implantation in highly mobile locations near joints. Design constraints during simulated transient swelling were verified in vitro. Maintenance of nerve health in various challenging anatomical locations (sciatic and median/ulnar nerves) was verified in a chronic feline model in vivo.