Brain Tissue Phantom Research Articles

Fabrication and Characterization of Brain Tissue Phantoms Using Agarose Gels for Ultraviolet Vision Systems.

Recreating cerebral tissue using a tissue-mimicking phantom is valuable because it provides a tool for studying physiological and biological processes related to tissues without the necessity of performing the study directly in the tissue or even in a patient. The reproduction of the optical properties allows investigation in areas such as imaging, optics, and ultrasound, among others. This paper presents a methodology for manufacturing agarose-based phantoms that mimic the optical characteristics of brain tissue using scattering and absorbing agents and proposes combinations of these agents to recreate the healthy brain tissue optical coefficients within the wavelength range of 350 to 500 nm. The results of the characterization of the manufactured phantoms propose ideal combinations of the used materials for their use in controlled environment experiments in the UV range, following a cost-effective methodology.

Method for optimizing imaging parameters to record neuronal and cellular activity at depth with bioluminescence.

Optical imaging has accelerated neuroscience in recent years. Genetically encoded fluorescent activity sensors of calcium, neurotransmitters, and voltage are commonly used for optical recording of neuronal activity. However, fluorescence imaging is limited to superficial regions for in vivo activity imaging, due to photon scattering and absorbance. Bioluminescence imaging offers a promising alternative for achieving activity imaging in deeper brain regions without hardware implanted within the brain. Bioluminescent reporters can be genetically encoded and produce photons without external excitation. The use of enzymatic photon production also enables prolonged imaging sessions without the risk of photobleaching or phototoxicity, making bioluminescence suitable for non-invasive imaging of deep neuronal populations. To facilitate the adoption of bioluminescent activity imaging, we sought to develop a low cost, simple in vitro method that simulates in vivo conditions to optimize imaging parameters for determining optimal exposure times and optical hardware configurations to determine what frame rates can be captured with an individual lab's imaging hardware with sufficient signal-to-noise ratios without the use of animals prior to starting an in vivo experiment. We developed an assay for modeling in vivo optical conditions with a brain tissue phantom paired with engineered cells that produce bioluminescence. We then used this assay to limit-test the detection depth versus maximum frame rate for bioluminescence imaging at experimentally relevant tissue depths using off-the-shelf imaging hardware. We developed an assay for modeling in vivo optical conditions with a brain tissue phantom paired with engineered cells that produce bioluminescence. With this method, we demonstrate an effective means for increasing the utility of bioluminescent tools and lowering the barrier to adoption of bioluminescence activity imaging. We demonstrated an improved method for optimizing imaging parameters for activity imaging in vivo with bioluminescent sensors.

Magnetic needle steering control using Lyapunov redesign

Using steerable needles to enable course correction and curved trajectories can improve surgical outcomes in numerous clinical interventions including electrode placement for deep brain stimulation. In this work, a physically motivated kinematic model for an actively steered magnetic-tipped needle is used in closed-loop control to perform insertion trajectories. The applied control law is derived using the Lyapunov redesign. Simulation results show this control method to be accurate for a wide range of conditions including randomized target trajectories. Control is performed experimentally in a brain tissue phantom for both initial position offset recovery and curved trajectories. Converged error results average 0.52 mm from target trajectory. Simulation results demonstrate the robustness of the control implementation, while experimental results exceed the accuracy required for the target application, encouraging future use in a clinical setting. Beyond needle insertion, this work has implications in general vehicle steering, as this model and control can apply to systems with similar kinematics such as boats and wheeled vehicles that could benefit from a relaxed slip constraint.

Investigations on correlations between changes of optical tissue properties and NMR relaxation times

BackgroundAccurate light dosimetry is a complex remaining challenge in interstitial photodynamic therapy (iPDT) for malignant gliomas. The light dosimetry should ideally be based on the tissue morphology and the individual optical tissue properties of each tissue type in the target region. First investigations are reported on using NMR information to estimate changes of individual optical tissue properties. MethodsPorcine brain tissue and optical tissue phantoms were investigated. To the porcine brain, supplements were added to simulate an edema or high blood content. The tissue phantoms were based on agar, Lipoveneous, ink, blood and gadobutrol (Gd-based MRI contrast agent). The concentrations of phantom ingredients and tissue additives are varied to compare concentration-dependent effects on optical and NMR properties. A 3-tesla whole-body MRI system was used to determine T1 and T2 relaxation times. Optical tissue properties, i.e., the spectrally resolved absorption and reduced scattering coefficient, were obtained using a single integrating sphere setup. The observed changes of NMR and optical properties were compared to each other. ResultsBy adjusting the NMR relaxation times and optical tissue properties of the tissue phantoms to literature values, recipes for human brain tumor, white matter and grey matter tissue phantoms were obtained that mimic these brain tissues simultaneously in both properties. For porcine brain tissue, it was observed that with increasing water concentration in the tissue, both NMR-relaxation times increased, while µa decreased and µs’ increased at 635 nm. The addition of blood to porcine brain samples showed a constant T1, while T2 shortened and the absorption coefficient at 635 nm increased. ConclusionsIn this investigation, by changing sample contents, notable changes of both NMR relaxation times and optical tissue properties have been observed and their relations examined. The developed dual NMR/optical tissue phantoms can be used in iPDT research, clinical training and demonstrations.

Agarose Gel Characterization for the Fabrication of Brain Tissue Phantoms for Infrared Multispectral Vision Systems.

Synthetic phantoms that recreate the characteristics of biological tissues are valuable tools for systematically studying and comprehending physiologies, pathologies, and biological processes related to tissues. The reproduction of mechanical and optical properties allows for the development and evaluation of novel systems and applications in areas such as imaging, optics, ultrasound, or dosimetry, among others. This paper proposes a methodology for manufacturing agarose-based phantoms that mimics the optical properties of healthy brain tissue within the wavelength infrared range of 800 to 820 nm. The fabrication of such phantoms enables the possibility of testing and experimentation in controlled and safe environments toward the design of new near-infrared multispectral imaging systems in neurosurgery. The results of an experimental optical characterization study indicate the validity and reliability of the proposed method for fabricating brain tissue phantoms in a cost-effective and straightforward fashion.

Quantitative monitoring and modelling of retrodialysis drug delivery in a brain phantom

A vast number of drug molecules are unable to cross the blood-brain barrier, which results in a loss of therapeutic opportunities when these molecules are administered by intravenous infusion. To circumvent the blood-brain barrier, local drug delivery devices have been developed over the past few decades such as reverse microdialysis. Reverse microdialysis (or retrodialysis) offers many advantages, such as a lack of net volume influx to the intracranial cavity and the ability to sample the tumour’s micro-environment. However, the translation of this technique to efficient drug delivery has not been systematically studied. In this work, we present an experimental platform to evaluate the performance of microdialysis devices in reverse mode in a brain tissue phantom. The mass of model drug delivered is measured by computing absorbance fields from optical images. Concentration maps are reconstructed using a modern and open-source implementation of the inverse Abel transform. To illustrate our method, we assess the capability of a commercial probe in delivering methylene blue to a gel phantom. We find that the delivery rate can be described by classical microdialysis theory, except at low dialysate flow rates where it is impacted by gravity, and high flow rates where significant convection to the gel occurs. We also show that the flow rate has an important impact not only on the overall size of the drug plume, but also on its shape. The numerical tools developed for this study have been made freely available to ensure that the method presented can be used to rapidly and inexpensively optimise probe design and protocol parameters before proceeding to more in-depth studies.

Convection-enhanced delivery with controlled catheter movement: A parametric finite element analysis.

Convection-enhanced delivery (CED) is an investigational method for delivering therapeutics directly to the brain for the treatment of glioblastoma. However, it has not become a common clinical therapy due to an inability of CED treatments to deliver therapeutics in a large enough tissue volume to fully saturate the target region. We have recently shown that the combination of controlled catheter movement and constant pressure infusions can be used to significantly increase volume dispersed (Vd ) in an agarose gel brain tissue phantom. In the present study, we develop a computational model to predict Vd achieved by various retraction rates with both constant pressure and constant flow rate infusions. An increase in Vd is achieved with any movement rate, but increase in Vd between successive movement rates drops off at rates above 0.3-0.35 mm/min. Finally, we found that infusions with retraction result in a more even distribution in concentration level compared to the stationary catheter, suggesting a potential increased ability for moving catheters to have a therapeutic impact regardless of the required therapeutic concentration level.

Performance Evaluation of MRI Based on Newly Developed MRiLab Simulation Using Inversion Recovery Pulse Sequence with Various Inversion Times

Among the representative types of magnetic resonance imaging (MRI) sequences, inversion recovery (IR) can improve the ability to detect brain lesions. The purpose of this study was to confirm the MRI characteristics according to TI changes in IR sequences. In this study, the MRiLab simulation program a newly developed, well-validated program was used to quantitatively analyze image characteristics with respect to the TI value in the IR sequence. Brain tissue phantom and standard phantom images were acquired by changing the TI at 100-ms intervals from 100 to 2,500 ms. In brain tissue phantom images, signal intensity (SI) values showed the lowest signals at TI values of 400, 700, and 2,500 ms in the white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF), respectively. The contrast evaluated in CSF-WM was superior at 400 ms and the lowest at 1,800 ms. In addition, the contrast evaluated in WM-GM was superior at 400 ms and the lowest at 1,500 ms. In the case of the brain standard phantom, the SI and contrast showed the same tendency as brain tissue phantom. In conclusion, an appropriate TI value was derived for obtaining images with excellent SI and contrast between brain tissues using a newly developed simulation program.

Constant Pressure Convection-Enhanced Delivery Increases Volume Dispersed With Catheter Movement in Agarose.

Convection-enhanced delivery (CED) has been extensively studied for drug delivery to the brain due to its inherent ability to bypass the blood-brain barrier. Unfortunately, CED has also been shown to inadequately distribute therapeutic agents over a large enough targeted tissue volume to be clinically beneficial. In this study, we explore the use of constant pressure infusions in addition to controlled catheter movement as a means to increase volume dispersed (Vd) in an agarose gel brain tissue phantom. Constant flow rate and constant pressure infusions were conducted with a stationary catheter, a catheter retracting at a rate of 0.25 mm/min, and a catheter retracting at a rate of 0.5 mm/min. The 0.25 mm/min and 0.5 mm/min retracting constant pressure catheters resulted in significantly larger Vd compared to any other group, with a 105% increase and a 155% increase compared to the stationary constant flow rate catheter, respectively. These same constant pressure retracting infusions resulted in a 42% and 45% increase in Vd compared to their constant flow rate counterparts. Using constant pressure infusions coupled with controlled catheter movement appears to have a beneficial effect on Vd in agarose gel. Furthermore, constant pressure infusions reveal the fundamental limitation of flow-driven infusions in both controlled catheter movement protocols as well as in stationary protocols where maximum infusion volume can never be reliably obtained.

The Development of Monolithic Silicon Carbide Intracortical Neural Interfaces for Long-Term Human Implantation

Silicon Carbide (SiC) has been demonstrated as both a bio- and neuro-compatible wide-band-gap semiconductor with a high thermal conductivity and magnetic susceptibility and may be potentially compatible with human brain tissue. Two single-crystal, solid-state forms of SiC have been used to create monolithic intracortical neural implants (INI) without using physiologically exposed metals or polymers, thus eliminating many known reliability challenges in-vivo through a single, homogenous material. Amorphous SiC (a-SiC) was used to insulate 16-channel functional INI and the electrochemical and MRI compatibility (7T) performance were measured. 4H-SiC interfaces were fabricated using homoepitaxy,alternating epitaxial films of n-type and p-type forming an isolating PN junction which prevents substrate leakage current between the 16 adjacent electrodes and traces fabricated which were formed using deep-reactive ion etching (DRIE). 3C-SiC interfaces were fabricated in a similar fashion, but the epitaial conductive layers were grown on on both bulk crystalline (100) silicon and SOI wafers. In both cases a conformal coating of a-SiC was used as the top-side insulator and windows opened using RIE to allow electrochemical interaction. Electrochemical charaterization achieved through electrochemcial impedance spectroscopy (EIS) and cyclic voltammetry (CV) indicates performance on par, or exceeding, that of Pt reference electrodes with the same form fit. While magnetic resonance imaging (MRI) is an essential, non-contact method used to investigate issues with the nervous system, the high field MRI (e.g., 3 T and higher) necessary for proper diagnosis can be a safety issue for patients with INI due to inductive coupling between the powerful electromagnetic fields and the implanted device. This results in having to use lower electromagnetic field power (less than 1.5T), and therefore lower resolution, which hinders diagnostic prognosis for these patients. In this work the MRI compliance of epitaxial, monolithic SiC INI was studied. The specific absorption rate (SAR), induced heating, and image artifacts caused by the portion of the implant within a brain tissue phantom located in a 7 T small animal MRI machine were estimated and measured via finite element method (FEM) and Fourier-based simulations. Both the simulation and experimental results revealed that free-standing 3C-SiC films had no observable image artifacts compared to silicon and platinum reference materials inside the MRI at 7 T while FEM simulations predicted an ~30% SAR reduction for 3C-SiC compared to Pt. These initial simulations and experiments indicate a SiC monolithic INI may effectively reduce MRI induced heating and image artifacts in high field MRI.

Experimental and simulation studies of localization and decoding of single and double dipoles

Objective. Electroencephalography is a technique for measuring normal or abnormal neuronal activity in the human brain, but its low spatial resolution makes it difficult to locate the precise locations of neurons due to the volume conduction effect of brain tissue. Approach. The acoustoelectric (AE) effect has the advantage of detecting electrical signals with high temporal resolution and focused ultrasound with high spatial resolution. In this paper, we use dipoles to simulate real single and double neurons, and further investigate the localization and decoding of single and double dipoles based on AE effects from numerical simulations, brain tissue phantom experiments, and fresh porcine brain tissue experiments. Main results. The results show that the localization error of a single dipole is less than 0.3 mm, the decoding signal is highly correlated with the source signal, and the decoding accuracy is greater than 0.94; the location of double dipoles with an interval of 0.4 mm or more can be localized, the localization error tends to increase as the interval of dipoles decreases, and the decoding accuracy tends to decrease as the frequency of dipoles decreases. Significance. This study localizes and decodes dipole signals with high accuracy, and provides a technical method for the development of EEG.

Sulcal Cavitation in Linear Head Acceleration: Possible Correlation With Chronic Traumatic Encephalopathy.

Traumatic Brain Injury (TBI) is a significant public health and financial concern that is affecting tens of thousands of people in the United States annually. There were over a million hospital visits related to TBI in 2017. Along with immediate and short-term morbidity from TBI, chronic traumatic encephalopathy (CTE) can have life-altering, chronic morbidity, yet the direct linkage of how head impacts lead to this pathology remains unknown. A possible clue is that chronic traumatic encephalopathy appears to initiate in the depths of the sulci. The purpose of this study was to isolate the injury mechanism/s associated with blunt force impact events. To this end, drop tower experiments were performed on a human head phantom. Our phantom was fabricated into a three-dimensional extruded ellipsoid geometry made out of Polyacrylamide gelatin that incorporated gyri-sulci interaction. The phantom was assembled into a polylactic acid 3D-printed skull, surrounded with deionized water, and enclosed between two optical windows. The phantom received repetitive low-force impacts on the order of magnitude of an average boxing punch. Intracranial pressure profiles were recorded in conjunction with high-speed imaging, 25 k frames-per-second. Cavitation was observed in all trials. Cavitation is the spontaneous formation of vapor bubbles in the liquid phase resulting from a pressure drop that reaches the vapor pressure of the liquid. The observed cavitation was predominately located in the contrecoup during negative pressure phases of local intracranial pressure. To further investigate the cavitation interaction with the brain tissue phantom, a 2D plane strain computational model was built to simulate the deformation of gyrated tissue as a result from the initiation of cavitation bubbles seen in the phantom experiments. These computational experiments demonstrated a focusing of strain at the depths of the sulci from bubble expansion. Our results add further evidence that mechanical interactions could contribute to the development of chronic traumatic encephalopathy and also that fluid cavitation may play a role in this interaction.

Development of a miniaturized and modular probe for fNIRS instrument.

Functional near-infrared spectroscopy (fNIRS) is a non-invasive and promising method for continuously monitoring hemodynamic and metabolic changes in tissues. However, the existing fNIRS equipment uses optical fiber, which is bulky, expensive, and time-consuming. We present a miniaturized, modular, novel silicon photomultiplier (SiPM) detector and develop a fNIRS instrument aimed at investigating the cerebral hemodynamic response for patients with epilepsy. Light emitting probe is a circle with a diameter of 5mm. Independent and modular light source and detector are more flexible in placement. The system can be expanded to high-density measurement with 16 light sources, 16 detectors, and 52 channels. The sampling rate of each channel is 25Hz. Instrument performance was evaluated using brain tissue phantom and in vivo experiments. High signal-to-noise ratio (60dB) in source detector separation (SDS) of 30mm, good stability (0.1%), noise equivalent power (0.89 pW), and system drift (0.56%) were achieved in the phantom experiment. Forearm blood-flow occlusion experiments were performed on the forearm of three healthy volunteers to demonstrate the ability to track rapid hemodynamic changes. Breath holding experiments on the forehead of healthy volunteers demonstrated the system can well detect brain function activity. The computer software was developed to display the original light signal intensity and the concentration changes of oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin (HbR) in real time. This system paves the way for our further diagnosis of epilepsy.

Highly hydroresponsive nacre-like oligo proanthocyanidin-intercalated Ca–Al-Layered double hydroxides/graphene oxide/polyvinyl alcohol as a potential neural implant material

Neural implantation with a microscale electrode permits a real-time neuromoduration to enhance the treatment of neural disorders. However, the penetration of a neural microprobe into soft brain tissues always resulted in the invasive tissue damage and mechanical tissue-device friction, which further induced the extensive chronic inflammation that limited the device lifetime. To develop a biocompatible and biocompliant neural implant, this study presented a smart substrate with bioinspired nacre-like structure that can exhibit ultra-hydroresponsive mechanical strength transition, sustained anti-inflammatory drug delivery, and anti-biofouling ability. An organic-inorganic composite, called LOG-P, was synthesized with oligo proanthocyanidin (OPC)-intercalated Ca–Al layered double hydroxide (Ca–Al-LDH) and graphene oxide (GO), followed by crosslinked with linear structural polyvinyl alcohol (PVA) to form a brick-and-mortar architecture. LOG-P exhibited strong mechanical strength of ~ 5 GPa in Young's modulus at dehydrated state, while showing ~99% decrease of Young's modulus when getting hydrated. In addition, the intercalation of OPC in LDH led to zero-order release with duration up to 80 days. LOG-P with negatively charged surfaces inhibited the adhesion of astrocytes, while the released OPC led to robust neuronal cell viability. Finally, integrated with Ag circuits by aerosol jet printing, the fabricated LOG-P-based microelectrode arrays showed stable electroactivity, also permitting a complete penetration into brain-tissue phantoms without bending. Such organic-inorganic nanocomposite-based neural interface with physical, chemical, and biological compatibility was expected to be a revolutionary platform for development of next-generation neural implants.

Silicon Carbide and MRI: Towards Developing a MRI Safe Neural Interface.

An essential method to investigate neuromodulation effects of an invasive neural interface (INI) is magnetic resonance imaging (MRI). Presently, MRI imaging of patients with neural implants is highly restricted in high field MRI (e.g., 3 T and higher) due to patient safety concerns. This results in lower resolution MRI images and, consequently, degrades the efficacy of MRI imaging for diagnostic purposes in these patients. Cubic silicon carbide (3C-SiC) is a biocompatible wide-band-gap semiconductor with a high thermal conductivity and magnetic susceptibility compatible with brain tissue. It also has modifiable electrical conductivity through doping level control. These properties can improve the MRI compliance of 3C-SiC INIs, specifically in high field MRI scanning. In this work, the MRI compliance of epitaxial SiC films grown on various Si wafers, used to implement a monolithic neural implant (all-SiC), was studied. Via finite element method (FEM) and Fourier-based simulations, the specific absorption rate (SAR), induced heating, and image artifacts caused by the portion of the implant within a brain tissue phantom located in a 7 T small animal MRI machine were estimated and measured. The specific goal was to compare implant materials; thus, the effect of leads outside the tissue was not considered. The results of the simulations were validated via phantom experiments in the same 7 T MRI system. The simulation and experimental results revealed that free-standing 3C-SiC films had little to no image artifacts compared to silicon and platinum reference materials inside the MRI at 7 T. In addition, FEM simulations predicted an ~30% SAR reduction for 3C-SiC compared to Pt. These initial simulations and experiments indicate an all-SiC INI may effectively reduce MRI induced heating and image artifacts in high field MRI. In order to evaluate the MRI safety of a closed-loop, fully functional all-SiC INI as per ISO/TS 10974:2018 standard, additional research and development is being conducted and will be reported at a later date.

Antifriction Mechanism of Longitudinal Vibration-Assisted Insertion in DBS

Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease. The insertion of brain tissue is an important procedure that affects the whole operation and the sequela. During the insertion process, the friction between the tissue and the needle shaft is the main factor affecting the degree of tissue damage and the accuracy of target location. Vibration-assisted needle insertion has been shown to reduce friction during needle insertion into biological tissue. LuGre model is a friction model that includes coulomb friction and viscous friction between two contact surfaces and accurately describes the Stribeck effect. This paper studies the influence of longitudinal vibration on the friction force during needle insertion. Based on LuGre model, the influence of longitudinal vibration parameters on friction force is discussed. Through experiments on porcine brain tissue and gel phantom, the friction force during insertion and the positive pressure of tissue against the needle under different vibration parameters were investigated. The experiment showed that the vibration can change the friction force by affecting the equivalent friction coefficient and the positive pressure of tissue against the needle. The equivalent friction coefficient showed a specific trend with the change of vibration parameters, while the positive pressure does not change with the vibration parameters.

EXTH-21. INTRAINFUSION CATHETER MOVEMENT FACILITATES INCREASED INFUSATE VOLUME DISPERSED IN AGAROSE GEL

Abstract Glioblastoma has a 5 year survival of only 5.5% and a median patient survival of 12 to 15 months even with gold standard treatment. One potential method of improving treatment of glioblastoma is the use of convection-enhanced delivery (CED) which utilizes local delivery of therapeutics to the brain. However, clinical trials have shown an inability of standard catheters to deliver therapeutics to the entire target area. In this study, we explore the potential of controlled catheter movement to increase the volume dispersed (Vd) of indigo carmine dye in agarose gel brain tissue phantoms. We use four catheter control protocols: stationary, continuous retraction, continuous insertion, and intermittent insertion using a single port stepped catheter. The continuous retraction group resulted in consistent catheter clogging caused by the continued insertion of the catheter and therefore was removed from further analysis. Vd and backflow distance was quantified for all other catheter movement protocols using optical images captured throughout the infusion. Catheter retraction resulted in an increase in Vd of 51% while intermittent insertion resulted in a Vd increase of 24% compared to the stationary catheter. Additionally, a 37% reduction in backflow distance was seen with the retracting catheter when compared to the stationary catheter. These results are further supported by a simplified computational model that we have created. The computational model simulates the infusion of indigo carmine dye through an agarose gel brain tissue phantom and shows an increase in Vd of over 100% with catheter retraction. The increased Vd and decreased backflow distance afforded by the retracting catheter, suggests that the use of catheter movement may be a useful technique in increasing drug dispersal in tumorous tissue. Additional work in live and excised tissue should be conducted to confirm these results and an exploration of optimal needle movement protocols is necessary.

Controlled Catheter Movement Affects Dye Dispersal Volume in Agarose Gel Brain Phantoms.

The standard of care for treatment of glioblastoma results in a mean survival of only 12 to 15 months. Convection-enhanced delivery (CED) is an investigational therapy to treat glioblastoma that utilizes locoregional drug delivery via a small-caliber catheter placed into the brain parenchyma. Clinical trials have failed to reach their endpoints due to an inability of standard catheters to fully saturate the entire brain tumor and its margins. In this study, we examine the effects of controlled catheter movement on dye dispersal volume in agarose gel brain tissue phantoms. Four different catheter movement control protocols (stationary, continuous retraction, continuous insertion, and intermittent insertion) were applied for a single-port stepped catheter capable of intrainfusion movement. Infusions of indigo carmine dye into agarose gel brain tissue phantoms were conducted during the controlled catheter movement. The dispersal volume (Vd), forward dispersal volume (Vdf), infusion radius, backflow distance, and forward flow distance were quantified for each catheter movement protocol using optical images recorded throughout the experiment. Vd and Vdf for the retraction and intermittent insertion groups were significantly higher than the stationary group. The stationary group had a small but significantly larger infusion radius than either the retracting or the intermittent insertion groups. The stationary group had a greater backflow distance and lower forward flow distance than either the retraction or the intermittent insertion groups. Continuous retraction of catheters during CED treatments can result in larger Vd than traditional stationary catheters, which may be useful for improving the outcomes of CED treatment of glioblastoma. However, catheter design will be crucial in preventing backflow of infusate up the needle tract, which could significantly alter both the Vd and shape of the infusion.

Customized Thinning of Silicon-based Neural Probes Down to 2 µm.

This paper reports on the customized thinning of neural probes based on silicon (Si) using deep reactive ion etching (DRIE) as a post-processing step. The reduced probe dimensions are expected to minimize local tissue trauma, while guaranteeing probe integrity during implantation. For DRIE, the probes are partially masked by a micromachined Si cover chip comprising tailored cavities enabling any desired thinned length l and probe thickness t by a proper choice of cover chip design and DRIE parameters, respectively. A broad variety of probe designs were realized with shank tip thicknesses ranging from 35 µm down to 2 µm. All probes could successfully be implanted into a brain tissue phantom, demonstrating a pronounced reduction in insertion force from 0.55 mN for unprocessed probes to 0.08 mN for 2-µm-thin shanks. When the dura mater was mimicked by a polyethylene (PE) membrane, forces were reduced from 28.9 mN to 16.6 mN for 15-µm-thin shanks.

Augmented reality visualization of hyperspectral imaging classifications for image-guided brain tumor phantom resection.

Wearable augmented reality (AR) is an emerging technology with enormous potential for use in the medical field, from training and procedure simulations to image-guided surgery. Medical AR seeks to enable surgeons to see tissue segmentations in real time. With the objective of achieving real-time guidance, the emphasis on speed produces the need for a fast method for imaging and classification. Hyperspectral imaging (HSI) is a non-contact, optical imaging modality that rapidly acquires hundreds of images of tissue at different wavelengths, which can be used to generate spectral data of the tissue. Combining HSI information and machine-learning algorithms allows for effective tissue classification. In this paper, we constructed a brain tissue phantom with porcine blood, yellow-dyed gelatin, and colorless gelatin to represent blood vessels, tumor, and normal brain tissue, respectively. Using a segmentation algorithm, hundreds of hyperspectral images were compiled to classify each of the pixels. Three segmentation labels were generated from the data, each with a different type of tissue. Our system virtually superimposes the HSI channels and segmentation labels of a brain tumor phantom onto the real scene using the HoloLens AR headset. The user can manipulate and interact with the segmentation labels and HSI channels by repositioning, rotating, changing visibility, and switching between them. All actions can be performed through either hand or voice controls. This creates a convenient and multifaceted visualization of brain tissue in real time with minimal user restrictions. We demonstrate the feasibility of a fast and practical HIS-AR technique for potential use of image-guided brain surgery.