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Abstract: Background context: In spinal fusion surgery, the accuracy with which screws are inserted in the pedicle has a direct effect on the surgical outcome. Accurate placement generally involves considerable judgmental skills that have been developed through a lengthy training process. Because the impact of misaligning one or more pedicle screws can directly affect patient safety, a number of navigational and trajectory verification approaches have been described and evaluated in the literature to provide some degree of guidance to the surgeon. Purpose: To provide a concise review to justify the need and explore the current state of developing navigational or trajectory verification techniques for ensuring proper pedicle screw insertion along with simulation methods for better educating the surgical trainees. Study design: Recent literature review. Methods: To justify the need to develop new methods for optimizing pedicle screw paths, we first reviewed some of the recent publications relating to the statistical outcomes for different types of navigation along with the conventional freehand (unassisted) screw insertion. Second, because of the importance of providing improved training in the skill of accurate screw insertion, the training aspects of relevant techniques are considered. The third part is devoted to the description of specific navigational assist methods or trajectory verification techniques and these include computer-assisted navigation, three-dimensional simulations, and also electric impedance and optical and ultrasonic image-guided methods. Conclusions: This article presents an overview of the need and the current status of the guidance methods available for improving the surgical outcomes in spinal fusion procedures. It also describes educational aids that have the potential for reducing the training process. [Copyright &y& Elsevier]

The identification of fast and slow waves propagating through trabecular bone is a challenging task due to temporal wave overlap combined with the high attenuation of the fast wave in the presence of noise. However, it can provide valuable information about bone integrity and become a means for monitoring osteoporosis. The objective of this work is to apply different coded excitation methods for this purpose. The results for single-sine cycle pulse, Golay code, and chirp excitations are compared. It is shown that Golay code is superior to the other techniques due to its signal enhancement while exhibiting excellent resolution without the ambiguity of sidelobes. [ABSTRACT FROM AUTHOR]

The optimal decompression time for patients presenting with acute traumatic central cord syndrome (ATCCS) has been debated, and a high level of evidence is lacking. To compare early (<24 hours) versus late (≥24 hours) surgical decompression for ATCCS. Systematic review and meta-analysis. Medline, PubMed, Embase, and CENTRAL were searched from inception to March 15th, 2023. The primary outcome was American Spinal Injury Association (ASIA) motor score. Secondary outcomes were venous thromboembolism (VTE), total complications, overall mortality, hospital length of stay (LOS), and ICU LOS. The GRADE approach determined certainty in evidence. The nine studies included reported on 5,619 patients, of whom 2,099 (37.35%) underwent early decompression and 3520 (62.65%) underwent late decompression. The mean age (53.3 vs 56.2 years, p=.505) and admission ASIA motor score (mean difference [MD]=−0.31 [−3.61, 2.98], p=.85) were similar between the early and late decompression groups. At 6-month follow-up, the two groups were similar in ASIA motor score (MD= −3.30 [−8.24, 1.65], p=.19). However, at 1-year follow-up, the early decompression group had a higher ASIA motor score than the late decompression group in total (MD=4.89 [2.89, 6.88], p<.001, evidence: moderate), upper extremities (MD=2.59 [0.82, 4.36], p=.004) and lower extremities (MD=1.08 [0.34, 1.83], p=.004). Early decompression was also associated with lower VTE (odds ratio [OR]=0.41 [0.26, 0.65], p=.001, evidence: moderate), total complications (OR=0.53 [0.42, 0.67], p<.001, evidence: moderate), and hospital LOS (MD=−2.94 days [−3.83, −2.04], p<.001, evidence: moderate). Finally, ICU LOS (MD=−0.69 days [−1.65, 0.28], p=.16, evidence: very low) and overall mortality (OR=1.35 [0.93, 1.94], p=.11, evidence: moderate) were similar between the two groups. The meta-analysis of these studies demonstrated that early decompression was beneficial in terms of ASIA motor score, VTE, complications, and hospital LOS. Furthermore, early decompression did not increase mortality odds. Although treatment decision-making has been individualized, early decompression should be considered for patients presenting with ATCCS, provided that the surgeon deems it appropriate. [ABSTRACT FROM AUTHOR]

Ultrasound technology can provide high-resolution imaging of blood flow following spinal cord injury (SCI). Blood flow imaging may improve critical care management of SCI, yet its duration is limited clinically by the amount of contrast agent injection required for high-resolution, continuous monitoring. In this study, we aim to establish non-contrast ultrasound as a clinically translatable imaging technique for spinal cord blood flow via comparison to contrast-based methods and by measuring the spatial distribution of blood flow after SCI. A rodent model of contusion SCI at the T12 spinal level was carried out using three different impact forces. We compared images of spinal cord blood flow taken using both non-contrast and contrast-enhanced ultrasound. Subsequently, we processed the images as a function of distance from injury, yielding the distribution of blood flow through space after SCI, and found the following. (1) Both non-contrast and contrast-enhanced imaging methods resulted in similar blood flow distributions (Spearman's ρ = 0.55, p < 0.0001). (2) We found an area of decreased flow at the injury epicenter, or umbra (p < 0.0001). Unexpectedly, we found increased flow at the periphery, or penumbra (rostral, p < 0.05; caudal, p < 0.01), following SCI. However, distal flow remained unchanged, in what is presumably unaffected tissue. (3) Finally, tracking blood flow in the injury zones over time revealed interesting dynamic changes. After an initial decrease, blood flow in the penumbra increased during the first 10 min after injury, while blood flow in the umbra and distal tissue remained constant over time. These results demonstrate the viability of non-contrast ultrasound as a clinical monitoring tool. Furthermore, our surprising observations of increased flow in the injury periphery pose interesting new questions about how the spinal cord vasculature reacts to SCI, with potentially increased significance of the penumbra. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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). Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma (GBM) is a common primary brain tumor with a short median overall survival despite aggressive treatment with resection, chemotherapy, and radiation therapy. Focused ultrasound (FUS) represents a promising new therapeutic approach for treatment of GBM. Unlike imaging forms of ultrasound, FUS can successfully penetrate the skull surrounding the brain, allowing for non-invasive ablation of tumor tissue. FUS can also temporarily disrupt the blood–brain barrier, a microvascular network that prohibits diffusion of most therapeutic agents, allowing chemotherapeutic drugs to penetrate the tumor. Other modalities are under investigation and include means of stimulating the immune system and sensitizing tumors to radiation therapy. The feasibility and safety of transcranial FUS has been illustrated in animal models and clinical trials. Precise results can be obtained under guidance from magnetic resonance imaging, limiting side effects. Successful outcomes from clinical trials will likely continue to motivate investigation and innovation of FUS technology for GBM. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Context: Cervical spondylosis may lead to spinal cord compression, poor vascular perfusion, and ultimately, cervical myelopathy. Studies suggest a neuroprotective effect of renin-angiotensin system (RAS) inhibitors in the brain, but limited data exist regarding their impact on the spinal cord.Purpose: To investigate whether RAS blockers and other antihypertensive drugs are correlated with preoperative functional status and imaging markers of cord compression in patients with symptomatic cervical spondylosis.Study Design: Retrospective observational study.Patient Sample: Individuals with symptomatic degenerative cervical stenosis who underwent surgery.Outcome Measures: Imaging features of spinal cord compression and functional status (modified Japanese Orthopedic Association [mJOA] and Nurick grading scales).Methods: Two hundred sixty-six operative patients with symptomatic degenerative cervical stenosis were included. Demographic data, comorbidities, antihypertensive medications, and functional status (including mJOA and Nurick grading scales) were collected. We evaluated canal compromise, cord compromise, surface area of T2 signal cord change, and pixel intensity of signal cord change compared with normal cord on T2-weighted magnetic resonance imaging sequences.Results: Of 266 patients, 41.7% were women, 58.3% were men; median age was 57.2 years; 20.6% smoked tobacco; 24.7% had diabetes mellitus. One hundred forty-nine patients (55.8%) had hypertension, 142 (95.3%) of these were taking antihypertensive medications (37 angiotensin-II receptor blockers [ARBs], 44 angiotensin-converting enzyme inhibitors, and 61 other medications). Patients treated with ARBs displayed a higher signal intensity ratio (ie, less signal intensity change in the compressed cord area) compared with untreated patients without hypertension (p=.004). Patients with hypertension had worse preoperative mJOA and Nurick scores than those without (p<.001). In the multivariate analysis, ARBs remained an independent beneficial factor for lower signal intensity change (p=.04), whereas hypertension remained a risk factor for worse preoperative neurological status (p<.01).Conclusions: In our study, patients with hypertension who were treated with RAS inhibitors had decreased T2-weighted signal intensity change than untreated patients without hypertension. Patients with hypertension also had worse preoperative functional status. Prospective case-control studies may deepen understanding of RAS modulators in the imaging and functional status of chronic spinal cord compression. [ABSTRACT FROM AUTHOR]

Pathologic thrombosis kills more people than cancer and trauma combined; it is associated with significant disability and morbidity, and represents a major healthcare burden. Despite advancements in medical therapies and imaging, there is often incomplete resolution of the thrombus. The residual thrombus can undergo fibrotic changes over time through infiltration of fibroblasts from the surrounding tissues and eventually transform into a permanent clot often associated with post-thrombotic syndrome. In order to understand the importance of cellular interactions and the impact of potential therapeutics to treat thrombosis, an in vitro platform using human cells and blood components would be beneficial. Towards achieving this aim, there have been studies utilizing the capabilities of microdevices to study the hemodynamics associated with thrombosis. In this work, we further exploited the utilization of 3D bioprinting technology, for the construction of a highly biomimetic thrombosis-on-a-chip model. The model consisted of microchannels coated with a layer of confluent human endothelium embedded in a gelatin methacryloyl (GelMA) hydrogel, where human whole blood was infused and induced to form thrombi. Continuous perfusion with tissue plasmin activator led to dissolution of non-fibrotic clots, revealing clinical relevance of the model. Further encapsulating fibroblasts in the GelMA matrix demonstrated the potential migration of these cells into the clot and subsequent deposition of collagen type I over time, facilitating fibrosis remodeling that resembled the in vivo scenario. Our study suggests that in vitro 3D bioprinted blood coagulation models can be used to study the pathology of fibrosis, and particularly, in thrombosis. This versatile platform may be conveniently extended to other vascularized fibrotic disease models. [ABSTRACT FROM AUTHOR]

Abstract: Biomaterials have emerged as powerful regulators of the cellular microenvironment for drug discovery, tissue engineering research and chemical testing. Although biomaterial-based matrices control the cellular behavior, these matrices are still far from being optimal. In principle, efficacy of biomaterial development for the cell cultures can be improved by using high-throughput techniques that allow screening of a large number of materials and manipulate microenvironments in a controlled manner. Several cell responses such as toxicity, proliferation, and differentiation have been used to evaluate the biomaterials thus providing basis for further selection of the lead biomimetic materials or microenvironments. Although high-throughput techniques provide an initial screening of the desired properties, more detailed follow-up studies of the selected materials are required to understand the true value of a ‘positive hit’. High-throughput methods may become important tools in the future development of biomaterials-based cell cultures that will enable more realistic pre-clinical prediction of pharmacokinetics, pharmacodynamics, and toxicity. This is highly important, because predictive pre-clinical methods are needed to improve the high attrition rate of drug candidates during clinical testing. [Copyright &y& Elsevier]

• An ultrasound-guided, focused ultrasound prototype was developed and validated. • The therapeutic transducer (1.5 MHz) consisted of three 8-mm circular elements. • Elements were placed on a 9 × 32mm curved rectangular aperture: 45 mm radius curvature. • Functionality was examined on tissue-mimicking phantoms. • 2.5 × 1.2 × 6.5 mm and 3.4 × 3.25 × 9.36 mm lesions were seen for 10 and 30 s sonification. To improve patient outcomes (eg, reducing blood loss and infection), practitioners have gravitated toward noninvasive and minimally invasive surgeries (MIS), which demand specialized toolkits. Focused ultrasound, for example, facilitates thermal ablation from a distance, thereby reducing injury to surrounding tissue. Focused ultrasound can often be performed noninvasively; however, it is more difficult to carry out in neuro-oncological tumors, as ultrasound is dramatically attenuated while propagating through the skull. This shortcoming has prompted exploration of MIS options for intracranial placement of focused ultrasound probes, such as within the BrainPath™ (NICO Corporation, Indianapolis, IN). Herein, we present the design, development, and in vitro testing of an image-guided, focused ultrasound prototype designed for use in MIS procedures. This probe can ablate neuro-oncological lesions despite its small size. Preliminary prototypes were iteratively designed, built, and tested. The final prototype consisted of three 8-mm-diameter therapeutic elements guided by an imaging probe. Probe functionality was validated on a series of tissue-mimicking phantoms. Lesions were created in tissue-mimicking phantoms with average dimensions of 2.5 × 1.2 × 6.5 mm and 3.4 × 3.25 × 9.36 mm after 10- and 30-second sonification, respectively. 30 s sonification with 118 W power at 50% duty cycle generated a peak temperature of 68 °C. Each ablation was visualized in real time by the built-in imaging probe. We developed and validated an ultrasound-guided focused ultrasound probe for use in MIS procedures. The dimensional constraints of the prototype were designed to reflect those of BrainPath trocars, which are MIS tools used to create atraumatic access to deep-seated brain pathologies. [ABSTRACT FROM AUTHOR]

Cervical spondylosis may lead to spinal cord compression, poor vascular perfusion, and ultimately cervical myelopathy. The process whereby chronic compression may cause spinal cord damage has not been fully understood. However, multiple mechanisms such as inflammation, apoptosis, and vascular variations, are thought to be responsible for the neuronal loss, axonal degeneration, and myelin impairment seen in cervical spondylotic myelopathy (CSM). Studies reported a beneficial effect of renin-angiotensin system (RAS) blockers in the central nervous system, particularly in brain inflammation and stroke, but data on their influence on the spinal cord are limited. We aimed to determine if RAS blockers are correlated with preoperative functional status and radiological markers of spinal cord damage secondary to compression in patients with CSM. Retrospective cohort study. Symptomatic cervical spondylosis patients. Functional status (including modified Japanese Orthopedic Association [mJOA] and Nurick grading scales) and imaging characteristics (including % maximum canal compromise [MCC], % maximum spinal cord compromise [MSCC], increased signal intensity [ISI], signal intensity ration [SIR] and ISI surface area), all of which were evaluated on midsagittal T2-weighted MRIs. Adults with symptomatic degenerative cervical stenosis patients were included. Demographic data, comorbidities, antihypertensive medications (particularly RAS blockers), and functional status were collected. We assessed % canal compromise, % cord compromise, surface area of T2 signal cord change, and pixel intensity of signal cord change compared to normal cord on T2-weighted MRI sequences. Of the 267 patients, 41.6% were female and 58.1% male; median age of 57.2 years; 20.6% smokers; 24.7% diabetics. One hundred forty-nine patients (55.8%) had hypertension, of which 142 (95.3%) were taking antihypertensive medications: 37 angiotensin-II receptor blockers [ARBs], 44 angiotensin-converting enzyme inhibitors [ACEIs], and 61 other medications). Patients treated with ARBs displayed a higher signal intensity ratio (lower signal intensity change in the compressed cord area) compared to those untreated non-hypertensive patients (p=.004). Hypertensive patients had worse preoperative mJOA and Nurick scores compared to non-hypertensive patients (p<.001). In the multivariate analysis, ARBs remained an independent beneficial factor for lower signal intensity change (p=.04), while hypertension remained a risk factor for worse preoperative neurological status (p<.01), after adjusting for covariables that were significant in the univariate analyses or were considered relevant. In cervical spinal cord compression patients, hypertensive subjects treated with RAS inhibitors were associated with less signal intensity change (higher SIR) than untreated non-hypertensive patients. Also, hypertensive subjects under any antihypertensive medication displayed worse mJOA and Nurick scores compared to untreated non-hypertensive individuals. Further studies are warranted to verify the effect of RAS inhibitors in spinal cord damage. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Purpose: The core needle biopsy (CNB) procedure is an essential part of breast cancer diagnosis. Current CNB devices on the market are not suitable for low-resource settings, which makes early breast cancer diagnosis inaccessible for women in these areas. Disposable CNB devices are the gold standard of breast cancer diagnostic tools in high-income countries, but the single-use cost—approximately $40 to $200—is unaffordable in low- and middle-income countries. Existing reusable devices are susceptible to internal contamination as blood travels back through the coaxial needle into the driver and thus requires laborious cleaning procedures. Methods: After conducting more than 100 interviews with stakeholders at 18 hospitals in the United States, South Africa, and Peru, we devised criteria for the device. The device must prevent internal driver contamination and match the standard tissue sample size. We report the design and development of a reusable CNB device with disposable needles that trap contamination. To demonstrate where blood travels in current reusable devices and prove that internal contamination can be completely eliminated, we created an external attachment that interfaces with the Bard Magnum, an existing reusable driver that yields internal contamination. To prove our concept, we evaluated contamination rates by placing water-indicating tape inside the Bard driver and firing the device into a plastic test tube that was filled with blood-mimicking solutions and covered with a latex glove. Results: When we fired the existing Bard Magnum device without our attachment, contaminants entered the internal compartment of the device both times, as shown by the water-indicating tape; however, when the device was fired with our external needle attachment, the water-indicating tape was completely clean, which verified that there was no internal contamination. Conclusion: We can conclude from our contamination testing that blood enters the device as a result of contaminants traveling back between the faces of the needle and sheath into the device's driver and that our external attachment eliminates this risk. Using these insights, we are currently developing a full reusable driver device with novel disposable needles that trap contamination to remove safety concerns associated with reusable devices, lower procedural cost, and increase access to breast cancer diagnostic tools in low-resource settings. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc. No COIs from the authors. [ABSTRACT FROM AUTHOR]