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Elastography is an imaging technology capable of measuring tissue stiffness and consistency. The technology has achieved widespread use in the workup and management of diseases of the liver, breast, thyroid, and prostate. Although elastography is increasingly being applied in neurosurgery, it has not yet achieved widespread adoption and many clinicians remain unfamiliar with the technology. Therefore, we sought to summarize the range of applications and elastography modalities available for neurosurgery, report its effectiveness in comparison with conventional imaging methods, and offer recommendations. All full-text English-language manuscripts on the use of elastography for neurosurgical procedures were screened using the PubMed/MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science databases. Thirty-two studies were included with 990 patients, including 21 studies on intracranial tumors, 5 on hydrocephalus, 4 on epilepsy, 1 on spinal cord compression, and 1 on adolescent scoliosis. Twenty studies used ultrasound elastography (USE) whereas 12 used magnetic resonance elastography (MRE). MRE studies were mostly used in the preoperative setting for assessment of lesion stiffness, tumor-brain adherence, diagnostic workup, and operative planning. USE studies were performed intraoperatively to guide resection of lesions, determine residual microscopic abnormalities, assess the tumor-brain interface, and study mechanical properties of tumors. Elastography can assist with resection of brain tissue, detection of microscopic lesions, and workup of hydrocephalus, among other applications under investigation. Its sensitivity often exceeds that of conventional MRI and ultrasound for identifying abnormal tissue and lesion margins.

Glioblastoma (GBM) is an aggressive primary astrocytoma associated with short overall survival. Treatment for GBM primarily consists of maximal safe surgical resection, radiation therapy, and chemotherapy using temozolomide. Nonetheless, recurrence and tumor progression is the norm, driven by tumor stem cell activity and a high mutational burden. Focused ultrasound (FUS) has shown promising results in preclinical and clinical trials for treatment of GBM and has received regulatory approval for the treatment of other neoplasms. Here, we review the range of applications for FUS in the treatment of GBM, which depend on parameters, including frequency, power, pulse duration, and duty cycle. Low-intensity FUS can be used to transiently open the blood–brain barrier (BBB), which restricts diffusion of most macromolecules and therapeutic agents into the brain. Under guidance from magnetic resonance imaging, the BBB can be targeted in a precise location to permit diffusion of molecules only at the vicinity of the tumor, preventing side effects to healthy tissue. BBB opening can also be used to improve detection of cell-free tumor DNA with liquid biopsies, allowing non-invasive diagnosis and identification of molecular mutations. High-intensity FUS can cause tumor ablation via a hyperthermic effect. Additionally, FUS can stimulate immunological attack of tumor cells, can activate sonosensitizers to exert cytotoxic effects on tumor tissue, and can sensitize tumors to radiation therapy. Finally, another mechanism under investigation, known as histotripsy, produces tumor ablation via acoustic cavitation rather than thermal effects.

Traumatic spinal cord injury (SCI) is a common and devastating condition. In the absence of effective validated therapies, there is an urgent need for novel methods to achieve injury stabilization, regeneration, and functional restoration in SCI patients. Ultrasound is a versatile platform technology that can provide a foundation for viable diagnostic and therapeutic interventions in SCI. In particular, real-time perfusion and inflammatory biomarker monitoring, focal pharmaceutical delivery, and neuromodulation are capabilities that can be harnessed to advance our knowledge of SCI pathophysiology and to develop novel management and treatment options. Our review suggests that studies that evaluate the benefits and risks of ultrasound in SCI are severely lacking and our understanding of the technology's potential impact remains poorly understood. Although the complex anatomy and physiology of the spine and the spinal cord remain significant challenges, continued technological advances will help the field overcome the current barriers and bring ultrasound to the forefront of SCI research and development.

Universalized point-of-care medicine demands long-term, automated, and ubiquitous solutions to monitoring patients. Ultrasound imaging can be found in nearly all fields of healthcare. Therefore, developing a platform for continuous ultrasound acquisition could transform the point-of-care arena. However, long-term monitoring using ultrasound imaging requires both the simplification of large quantities of data and a hands-free, flexible device. Here, we reduce data-heavy spectral Doppler imaging by tracking local vascular flow in vitro and in vivo as a single, clinically interpretable value over time. Imaging is performed using a novel probe designed specifically for continuous monitoring with ultrasound. This semi-conformal specialty probe was fabricated by removing the plastic casing of a commercially available probe, bending the tip of the piezoelectric transducer head at a nearly ninety-degree angle, then casting the electronic components in silicone rubber, which allowed the probe to rest comfortably on any surface. No statistically significant difference existed when comparing the Doppler fluid velocity detected by the specialty probe with two commercial probes, where velocity directly leads to calculation of vascular flow. Additionally, continuously tracked velocity over the period of an hour and during periods of fluctuating flow rates demonstrated the potential for accurate, long-term monitoring using this ultrasound device. Thus, translating this technology from bench to bedside could provide a universal solution to point-of-care medicine.

Glioblastoma Multiforme (GBM) is a malignant brain cancer with low overall survival. Therefore, researchers are looking to augment its current therapeutic regimen, which includes surgical tumor resection, chemotherapy and radiation. A promising treatment modality, focused ultrasound, has been used as a non-invasive treatment for GBM through multiple approaches such as thermal ablation, immunomodulation, and blood brain barrier disruption. In order to develop these treatments for clinical trials, testing in animal models needs to be performed to investigate the efficacy of the treatment in complex biological environments, as well as to evaluate any side-effects. The more biologically relevant the animal model is to human anatomy, the more applicable the results will be for translation to clinical trials. Here, we report a human GBM rat model, which utilizes an IDH-wildtype, EGFRvIII mutant patient-derived xenograft in athymic rats. The in vivo tumor growth rate was assessed over a period of 20 days to evaluate reproducibility and to develop the model for future testing of FUS in the treatment of GBM.

Focused ultrasound (FUS) is becoming widely researched for medical therapies due to its high penetration depth, spatial resolution, and affordability. Applications of FUS range from high intensity focused ultrasound (HIFU) for the ablation of cancerous tumors to low intensity focused ultrasound (LIFU) for the treatment of neurological conditions like essential tremors. A key step in developing these treatments and their corresponding FUS devices is characterizing the emitted ultrasound from the proposed transducer. However, a bottleneck exists at this verification and validation stage; current characterization techniques lack the robustness of reliably recording below a 5μm resolution. This level of accuracy is needed to adequately design devices which can target cells like astrocytes or other desired target tissues at this scale. Our Acoustic Measurement Platform for Localizing and Implementing Therapeutic Ultrasound Devices and Equipment (AMPLITUDE) is a solution which enables engineers, scientists, and clinicians to confidently characterize their equipment in a benchtop setting. It achieves this resolution by utilizing an all-in-one water conditioning unit, linear stepper motors with a theoretical step size of 1 μm and a 1% standard deviation on repetitive experiments, as well as signal processing techniques. This system can be used throughout the product timeline including prototyping, verifying efficacy, FDA testing, and routine check-ups during clinical use.

Focused ultrasound (FUS) is an emerging technique with the potential to revolutionize traditional treatment methods in the fields of oncology and neurosurgery. Recently, FUS treatments have shown potential for altering neural activity in the spinal cord, with the intent to alleviate pain. Preliminary animal studies using FUS have demonstrated the need for transducer accessories that can simplify the implementation of the transducer in the clinic. The coupling cone that was supplied with the transducer was designed for larger target tissues. Thus, surgeons have expressed a desire to adapt the cone design to be easier to use for smaller targets, such as the spinal cord. Here, we developed 3D printed cones, with smaller aperture sizes, for FUS transducers to assist surgeons in localizing the focal point of the transducers in a faster, and more intuitive manner. The cones were designed to not alter the original focal region of the transducers. This was experimentally confirmed by measuring the size of the focal region for the transducer with the new cones and comparing this data to measurements provided by the manufacturer. The new coupling cones will make the FUS transducers more ergonomic for use in stimulating the spinal cord in an animal model.

Monitoring microcirculation and visualizing microvasculature are critical for providing diagnosis to medical professionals and guiding clinical interventions. Ultrasound provides a medium for monitoring and visualization; however, there are challenges due to the complex microscale geometry of the vasculature and difficulties associated with quantifying perfusion. Here, we studied established and state-of-the-art ultrasonic modalities (using six probes) to compare their detection of slow flow in small microvasculature.Five ultrasonic modalities were studied: grayscale, color Doppler, power Doppler, superb microvascular imaging (SMI), and microflow imaging (MFI), using six linear probes across two ultrasound scanners. Image readability was blindly scored by radiologists and quantified for evaluation. Vasculature visualization was investigated both in vitro (resolution and flow characterization) and in vivo (fingertip microvasculature detection).Superb Microvascular Imaging (SMI) and Micro Flow Imaging (MFI) modalities provided superior images when compared with conventional ultrasound imaging modalities both in vitro and in vivo. The choice of probe played a significant difference in detectability. The slowest flow detected (in the lab) was 0.1885 ml/s and small microvasculature of the fingertip were visualized.Our data demonstrated that SMI and MFI used with vascular probes operating at higher frequencies provided resolutions acceptable for microvasculature visualization, paving the path for future development of ultrasound devices for microcirculation monitoring.

Cotton balls are used in neurosurgical procedures to assist with hemostasis and improve vision within the operative field. Although the surgeon can reshape pieces of cotton for multiple intraoperative uses, this customizability and scale also places them at perpetual risk of being lost, as blood-soaked cotton balls are visually similar to raw brain tissue. Retained surgical cotton can induce potentially life-threatening immunologic responses, impair postoperative imaging, lead to a textiloma or misdiagnosis, and/or require reoperation. This study investigated three imaging modalities (optical, acoustic, and radiographic) to find the most effective method of identifying foreign bodies during neurosurgery. First, we examined the use of dyes to increase contrast between cotton and surrounding parenchyma (optical approach). Second, we explored the ability to distinguish surgical cotton on or below the tissue surface from brain parenchyma using ultrasound imaging (acoustic approach). Lastly, we analyzed the ability of radiography to differentiate between brain parenchyma and cotton. Our preliminary testing demonstrated that dark-colored cotton is significantly more identifiable than white cotton on the surface level. Additional testing revealed that cotton has noticeable different acoustic characteristics (eg, speed of sound, absorption) from neural tissue, allowing for enhanced contrast in applied ultrasound imaging. Radiography, however, did not present sufficient contrast, demanding further examination. These solutions have the potential to significantly reduce the possibility of intraoperative cotton retention both on and below the surface of the brain, while still providing surgeons with traditional cotton material properties without affecting the surgical workflow.

Total hip arthroplasty (THA) procedures have been identified as high-volume procedures with growing prevalence. During the procedure, orthopedic surgeons largely rely solely on qualitative assessment to ensure an excessive limb length discrepancy (LLD) is not introduced from the implant selection. LLD can result in back pain and gait complications, with some cases of LLD requiring a revision procedure to mitigate. To address this issue, we evaluated several methods of sensing distance intraoperatively to determine the best approach to measure leg length during the THA procedure. A testing setup using a sawbones model of hip anatomy in the decubitus position was used as a simulation of the THA procedure to test the accuracy of each of the sensing modalities.

Standard diagnostic ultrasound imaging procedures heavily rely on a sonographer for image acquisition. Given the ultrasound probe is manually manipulated by the sonographer, there is a potential for noise artifacts like blurry acquired images caused by involuntary hand movements. Certain surgical procedures can also cause patients to exhibit involuntary “jumping” movements while on the operating table leading to further deterioration in ultrasound image quality. In this study, we attempt to mitigate these problems by fabricating a 3D-printed ultrasound probe holder. Due to the lightweight nature of the device, it can attach to surgical retractors without influencing the functionality of the retractor. Therefore, the 3D printed probe holder not only reduces relative motion between the probe and the patient, but also reduce the need for a sonographer during complex surgeries.

Spinal cord injury (SCI) is a devastating condition that affects about 17,000 individuals every year in the United States, with approximately 294,000 people living with the ramifications of the initial injury. After the initial primary injury, SCI has a secondary phase during which the spinal cord sustains further injury due to ischemia, excitotoxicity, immune-mediated damage, mitochondrial dysfunction, apoptosis, and oxidative stress. The multifaceted injury progression process requires a sophisticated injury-monitoring technique for an accurate assessment of SCI patients. In this narrative review, we discuss SCI monitoring modalities, including pressure probes and catheters, micro dialysis, electrophysiologic measures, biomarkers, and imaging studies. The optimal next-generation injury monitoring setup should include multiple modalities and should integrate the data to produce a final simplified assessment of the injury and determine markers of intervention to improve patient outcomes.

Many surgeons are faced with inoperable or only partially operable brain lesions, such as tumors. Even when surgery is feasible, patient outcomes are greatly affected by blood loss or infection. This has led many physicians toward non- or minimally-invasive surgery, which demands specialized toolkits. Focused ultrasound has great potential for assisting in such procedures due to its ability to focus a few centimeters away from the surface of the transducer. In a prior study, we developed a focused ultrasound prototype that could fit within a BrainPath trocar, specifically made for minimally invasive brain surgery. Here, we present the design and fabrication of a second prototype that reduces size, is MR-compatible, and has electronic steering capabilities.

Transcranial focused ultrasound stimulation is a neuromodulation technique that is capable of exciting or suppressing the neural network. Such neuro-modulatory effects enable the treatment of brain diseases non-invasively, such as treating stroke. The neuro-modulatory effect on cerebral hemodynamics has been monitored using laser speckle contrast imaging in animal studies. However, the bulky size and stationary nature of the imaging system constrains the application of this imaging technique on research that requires the animal to have different body positions or to be awake. We present the design of a system that combines a miniature microscope for laser speckle contrast imaging and transcranial focused ultrasound stimulation, as well as, test its capability to monitor cerebral hemodynamics during stimulation and compare the result with a benchtop imaging system.

Access to deep-seated brain lesions (e.g., tumors, aneurysms, hematomas, and other malformations) is challenging due to the potential for retraction-induced injury. Traditionally, neurosurgeons use dissection and blade retractors to push apart tissue to visualize and operate on target lesions. These blades apply focal pressure onto the brain, resulting in ischemia, edema, and parenchymal trauma, leading to complications in up to 29% of cases. Tubular retractors were introduced to distribute forces radially and have led to improved safety and clinical outcomes. However, reports indicate that tubular retractors still led to complications in up to 9.1% of cases. Other concerns include significant pressure in the direction of insertion and the displacement of anatomic landmarks leading to inaccurate stereotaxis. We present a novel, minimally-invasive brain retractor that utilizes an expandable soft balloon to further reduce retraction-induced injury and increase stereotactic accuracy with a minimal port of entry. The device consists of a balloon catheter system, a clear sheath, and integration with neuronavigation stylets. This approach can reduce the rate of iatrogenic injury and improve clinical outcomes for brain lesion operations. Furthermore, we illustrate the efficacy of this device in use compared to those of conventional tubular and blade retractors in a pig cadaver.

Cotton balls are a versatile and efficient tool commonly used in neurosurgical procedures to absorb fluids and manipulate delicate tissues. However, the use of cotton balls is accompanied by the risk of accidental retention in the brain after surgery. Retained cotton balls can lead to dangerous immune responses and potential complications, such as adhesions and textilomas. In a previous study, we showed that ultrasound can be safely used to detect cotton balls in the operating area due to the distinct acoustic properties of cotton compared with the acoustic properties of surrounding tissue. In this study, we enhance the experimental setup using a 3D-printed custom depth box and a Butterfly IQ handheld ultrasound probe. Cotton balls were placed in variety of positions to evaluate size and depth detectability limits. Recorded images were then analyzed using a novel algorithm that implements recently released YOLOv4, a state-of-the-art, real-time object recognition system. As per the radiologists’ opinion, the algorithm was able to detect the cotton ball correctly 61% of the time, at approximately 32 FPS. The algorithm could accurately detect cotton balls up to 5mm in diameter, which corresponds to the size of surgical balls used by neurosurgeons, making the algorithm a promising candidate for regular intraoperative use.

Efficiency and patient safety are top priorities in any surgical operation. One effective way to achieve these objectives is automating many of the logistical and routine tasks that occur in the operating room. Inspired by smart assistant technology already commonplace in the consumer sector, we engineered the Smart Hospital Assistant (SHA), a smart, voice-controlled virtual assistant that handles natural speech recognition while executing a plurality of functions to aid surgery. Simulated surgeries showed that the SHA reduced operating time, optimized surgical staff resources, and reduced the number of major touch points that can lead to surgical site infections. The SHA not only shows its potential in the operating room, but also in other healthcare environments that may benefit from having virtual smart assistant technology.