Surgical Guidance Tool Research Articles

A hyperspectral surgical microscope with super-resolution reconstruction for intraoperative image guidance.

Hyperspectral imaging (HSI) is an emerging imaging modality in medical applications, especially for intraoperative image guidance. A surgical microscope improves surgeons' visualization with fine details during surgery. The combination of HSI and surgical microscope can provide a powerful tool for surgical guidance. However, to acquire high-resolution hyperspectral images, the long integration time and large image file size can be a burden for intraoperative applications. Super-resolution reconstruction allows acquisition of low-resolution hyperspectral images and generates high-resolution HSI. In this work, we developed a hyperspectral surgical microscope and employed our unsupervised super-resolution neural network, which generated high-resolution hyperspectral images with fine textures and spectral characteristics of tissues. The proposed method can reduce the acquisition time and save storage space taken up by hyperspectral images without compromising image quality, which will facilitate the adaptation of hyperspectral imaging technology in intraoperative image guidance.

An injectable fluorescent and iodinated hydrogel for preoperative localization and dual image-guided surgery of pulmonary nodules.

The widespread use of video-assisted thoracoscopic surgery (VATS) has triggered the rapid expansion in the field of computed tomography (CT)-guided preoperative localization and near-infrared (NIR) fluorescence image-guided surgery. However, its broader application has been hindered by the absence of ideal imaging contrasts that are biocompatible, minimally invasive, highly resolvable, and perfectly localized within the diseased tissue. To achieve this goal, we synthesize a dextran-based fluorescent and iodinated hydrogel, which can be injected into the tissue and imaged with both CT and NIR fluorescence modalities. By finely tuning the physical parameters such as gelation time and composition of iodinated oil (X-ray contrast agent) and indocyanine green (ICG, NIR fluorescence dye), we optimize the hydrogel for prolonged localization at the injected site without losing the dual-imaging capability. We validate the effectiveness of the developed injectable dual-imaging platform by performing image-guided resection of pulmonary nodules on tumor-bearing rabbits, which are preoperatively localized with the hydrogel. The injectable dual-imaging marker, therefore, can emerge as a powerful tool for surgical guidance.

Three-dimensional sonification as a surgical guidance tool

AbstractInteractive Sonification is a well-known guidance method in navigation tasks. Researchers have repeatedly suggested the use of interactive sonification in neuronavigation and image-guided surgery. The hope is to reduce clinicians’ cognitive load through a relief of the visual channel, while preserving the precision provided through image guidance. In this paper, we present a surgical use case, simulating a craniotomy preparation with a skull phantom. Through auditory, visual, and audiovisual guidance, non-clinicians successfully find targets on a skull that provides hardly any visual or haptic landmarks. The results show that interactive sonification enables novice users to navigate through three-dimensional space with a high precision. The precision along the depth axis is highest in the audiovisual guidance mode, but adding audio leads to higher durations and longer motion trajectories.

Anatomy-Specific Classification Model Using Label-Free FLIm to Aid Intraoperative Surgical Guidance of Head and Neck Cancer.

Intraoperative identification of head and neck cancer tissue is essential to achieve complete tumor resection and mitigate tumor recurrence. Mesoscopic fluorescence lifetime imaging (FLIm) of intrinsic tissue fluorophores emission has demonstrated the potential to demarcate the extent of the tumor in patients undergoing surgical procedures of the oral cavity and the oropharynx. Here, we report FLIm-based classification methods using standard machine learning models that account for the diverse anatomical and biochemical composition across the head and neck anatomy to improve tumor region identification. Three anatomy-specific binary classification models were developed (i.e., "base of tongue," "palatine tonsil," and "oral tongue"). FLIm data from patients (N = 85) undergoing upper aerodigestive oncologic surgery were used to train and validate the classification models using a leave-one-patient-out cross-validation method. These models were evaluated for two classification tasks: (1) to discriminate between healthy and cancer tissue, and (2) to apply the binary classification model trained on healthy and cancer to discriminate dysplasia through transfer learning. This approach achieved superior classification performance compared to models that are anatomy-agnostic; specifically, a ROC-AUC of 0.94 was for the first task and 0.92 for the second. Furthermore, the model demonstrated detection of dysplasia, highlighting the generalization of the FLIm-based classifier. Current findings demonstrate that a classifier that accounts for tumor location can improve the ability to accurately identify surgical margins and underscore FLIm's potential as a tool for surgical guidance in head and neck cancer patients, including those subjects of robotic surgery.

Interim clinical trial analysis of intraoperative mass spectrometry for breast cancer surgery

Optimal resection of breast tumors requires removing cancer with a rim of normal tissue while preserving uninvolved regions of the breast. Surgical and pathological techniques that permit rapid molecular characterization of tissue could facilitate such resections. Mass spectrometry (MS) is increasingly used in the research setting to detect and classify tumors and has the potential to detect cancer at surgical margins. Here, we describe the ex vivo intraoperative clinical application of MS using a liquid micro-junction surface sample probe (LMJ-SSP) to assess breast cancer margins. In a midpoint analysis of a registered clinical trial, surgical specimens from 21 women with treatment naïve invasive breast cancer were prospectively collected and analyzed at the time of surgery with subsequent histopathological determination. Normal and tumor breast specimens from the lumpectomy resected by the surgeon were smeared onto glass slides for rapid analysis. Lipidomic profiles were acquired from these specimens using LMJ-SSP MS in negative ionization mode within the operating suite and post-surgery analysis of the data revealed five candidate ions separating tumor from healthy tissue in this limited dataset. More data is required before considering the ions as candidate markers. Here, we present an application of ambient MS within the operating room to analyze breast cancer tissue and surgical margins. Lessons learned from these initial promising studies are being used to further evaluate the five candidate biomarkers and to further refine and optimize intraoperative MS as a tool for surgical guidance in breast cancer.

Optical coherence tomography of cranial dura mater: Microstructural visualization in vivo

PurposeThe study explores microscope integrated optical coherence tomography (OCT) as a intraoperative imaging technique to delineate the microstructural composition of human dura mater cranialis and underlying leptomeninges for surgical guidance. MethodsOCT volume scans, light microscopic pictures and light microscopic videos of the dura mater were acquired in patients (n = 20) with indication for craniotomy. OCT volume scans and corresponding light microscopic data were analyzed post procedural. Thickness of anatomical structures was measured during this phase. ResultsOCT scanning of the human cranial dura mater was feasible during microsurgical dissection. A discrimination of the endosteal and inner meningeal layer of the cranial dura mater was possible in 70 % (n = 14) of the patients. Transdural OCT scans could further demonstrate subdural anatomical structures: subdural space 10 % (n = 2), subarachnoid space in 35 % (n = 7), arachnoid vessels in 80 % (n = 16) and brain cortex in 90 % (n = 16) of the patients. Orthogonal distance measurement was possible. The cranial dura mater showed a mean depth of 216 μm, the endosteal layer of 120 μm and the inner meningeal layer of 132 μm. Imaging quality of the dural segment was high – approaching spatial resolution of histopathology. Imaging quality of subdural segments was lower and demonstrated A-line artifacts in 45 % (n = 7). ConclusionThese results illustrate - for the first time - strengths and weaknesses of three dimensional microscope integrated OCT as an in vivo imaging method of the human cranial dura mater, underlying leptomeninges and human brain cortex as a surgical guidance tool. OCT imaging of the cranial dura mater showed extensive details. Transdural imaging of subdural micro anatomical structures was possible, but showed lower image quality with intermittent A-line artifacts. OCT stated the first intraoperative imaging tool to measure the depth of micro anatomical structures with a high spatial resolution of 7,5 μm.

HYPerspectral Enhanced Reality (HYPER): a physiology-based surgical guidance tool.

HSI is an optical technology allowing for a real-time, contrast-free snapshot of physiological tissue properties, including oxygenation. Hyperspectral imaging (HSI) has the potential to quantify the gastrointestinal perfusion intraoperatively. This experimental study evaluates the accuracy of HSI, in order to quantify bowel perfusion, and to obtain a superposition of the hyperspectral information onto real-time images. In 6 pigs, 4 ischemic bowel loops were created (A, B, C, D) and imaged at set time points (from 5 to 360min). A commercially available HSI system provided pseudo-color maps of the perfusion status (StO2, Near-InfraRed perfusion) and the tissue water index. An ad hoc software was developed to superimpose HSI information onto the live video, creating the HYPerspectral-based Enhanced Reality (HYPER). Seven regions of interest (ROIs) were identified in each bowel loop according to StO2 ranges, i.e., vascular (VASC proximal and distal), marginal vascular (MV proximal and distal), marginal ischemic (MI proximal and distal), and ischemic (ISCH). Local capillary lactates (LCL), reactive oxygen species (ROS), and histopathology were measured at the ROIs. A machine-learning-based prediction algorithm of LCL, based on the HSI-StO2%, was trained in the 6 pigs and tested on 5 additional animals. HSI parameters (StO2 and NIR) were congruent with LCL levels, ROS production, and histopathology damage scores at the ROIs discriminated by HYPER. The global mean error of LCL prediction was 1.18 ± 1.35mmol/L. For StO2 values > 30%, the mean error was 0.3 ± 0.33. HYPER imaging could precisely quantify the overtime perfusion changes in this bowel ischemia model.

Multi-Parametric Standardization of Fluorescence Imaging Systems Based on a Composite Phantom.

Fluorescence molecular imaging (FMI) has emerged as a promising tool for surgical guidance in oncology, with one of the few remaining challenges being the ability to offer quality control and data referencing. This paper investigates the use of a novel composite phantom to correct and benchmark FMI systems. This paper extends on previous work by describing a phantom design that can provide a more complete assessment of FMI systems through quantification of dynamic range and determination of spatial illumination patterns for both reflectance and fluorescence imaging. Various performance metrics are combined into a robust and descriptive "system benchmarking score," enabling not only the comprehensive comparison of different systems, but also for the first time, correction of the acquired data. We show that systems developed for targeted fluorescence imaging can achieve benchmarking scores of up to 70%, while clinically available systems optimized for indocyanine green are limited to 50%, mostly due to greater leakage of ambient and excitation illumination and lower resolution. The image uniformity can also be approximated and employed for image flat-fielding, an important milestone toward data referencing. In addition, we demonstrate composite phantom use in assessing the performance of a surgical microscope and of a raster-scan imaging system. Our results suggest that the new phantom has the potential to support high-fidelity FMI through benchmarking and image correction. Standardization of the FMI is a necessary process for establishing good imaging practices in clinical environments and for enabling high-fidelity imaging across patients and multi-center imaging studies.

Biophysical basis of skin cancer margin assessment using Raman spectroscopy.

Achieving adequate margins during tumor margin resection is critical to minimize the recurrence rate and maximize positive patient outcomes during skin cancer surgery. Although Mohs micrographic surgery is by far the most effective method to treat nonmelanoma skin cancer, it can be limited by its inherent required infrastructure, including time-consuming and expensive on-site histopathology. Previous studies have demonstrated that Raman spectroscopy can accurately detect basal cell carcinoma (BCC) from surrounding normal tissue; however, the biophysical basis of the detection remained unclear. Therefore, we aim to explore the relevant Raman biomarkers to guide BCC margin resection. Raman imaging was performed on skin tissue samples from 30 patients undergoing Mohs surgery. High correlations were found between the histopathology and Raman images for BCC and primary normal structures (including epidermis, dermis, inflamed dermis, hair follicle, hair shaft, sebaceous gland and fat). A previously developed model was used to extract the biochemical changes associated with malignancy. Our results showed that BCC had a significantly different concentration of nucleus, keratin, collagen, triolein and ceramide compared to normal structures. The nucleus accounted for most of the discriminant power (90% sensitivity, 92% specificity - balanced approach). Our findings suggest that Raman spectroscopy is a promising surgical guidance tool for identifying tumors in the resection margins.

Optimizing fresh specimen staining for rapid identification of tumor biomarkers during surgery.

Rationale: Positive margin status due to incomplete removal of tumor tissue during breast conserving surgery (BCS) is a prevalent diagnosis usually requiring a second surgical procedure. These follow-up procedures increase the risk of morbidity and delay the use of adjuvant therapy; thus, significant efforts are underway to develop new intraoperative strategies for margin assessment to eliminate re-excision procedures. One strategy under development uses topical application of dual probe staining and a fluorescence imaging strategy termed dual probe difference specimen imaging (DDSI). DDSI uses a receptor-targeted fluorescent probe and an untargeted, spectrally-distinct fluorescent companion imaging agent topically applied to fresh resected specimens, where the fluorescence from each probe is imaged and a normalized difference image is computed to identify tumor-target distribution in the specimen margins. While previous reports suggested this approach is a promising new tool for surgical guidance, advancing the approach into the clinic requires methodical protocol optimization and further validation.Methods: In the present study, we used breast cancer xenografts and receiver operator characteristic (ROC) curve analysis to evaluate a wide range of staining and imaging parameters, and completed a prospective validation study on multiple tumor phenotypes with different target expression. Imaging fluorophore-probe pair, concentration, and incubation times were systematically optimized using n=6 tissue specimen replicates per staining condition. Resulting tumor vs. normal adipose tissue diagnostic performance were reported and staining patterns were validated via receptor specific immunohistochemistry colocalization. Optimal staining conditions were tested in receptor positive and receptor negative cohorts to confirm specificity.Results: The optimal staining conditions were found to be a one minute stain in a 200 nM probe solution (area under the curve (AUC) = 0.97), where the choice of fluorescent label combination did not significantly affect the diagnostic performance. Using an optimal threshold value determined from ROC curve analysis on a training data set, a prospective study on xenografts resulted in an AUC=0.95 for receptor positive tumors and an AUC = 0.50 for receptor negative (control) tumors, confirming the diagnostic performance of this novel imaging technique.Conclusions: DDSI provides a robust, molecularly specific imaging methodology for identifying tumor tissue over benign mammary adipose tissue. Using a dual probe imaging strategy, nonspecific accumulation of targeted probe was corrected for and tumor vs. normal tissue diagnostic potential was improved, circumventing difficulties with ex vivo tissue specimen staining and allowing for rapid clinical translation of this promising technology for tumor margin detection during BCS procedures.

Development of Insertion Models Predicting Cochlear Implant Electrode Position.

To assess the possibility to define a preferable range for electrode array insertion depth and surgical insertion distance for which frequency mismatch is minimalized. To develop a surgical insertion guidance tool by which a preferred target angle can be attained using preoperative available anatomical data and surgically controllable insertion distance. Multiplanar reconstructions of pre- and post-operative CT scans were evaluated in a population of 336 patients implanted with the CII HiFocus1 or HiFocus1J implant (26 bilaterally implantees included). Cochlear radial distances were measured on four measurement axes on the preoperative CT scan. Electrode contact positions were obtained in angular depth, distance from the round window and to the modiolus center. Frequency mismatch was calculated based on the yielded frequency as a function of the angular position per contact. Cochlear diameters were clustered into three cochlear size groups with K-sample clustering. Using spiral fitting and general linear regression modeling, the feasibility of different insertion models with cochlear size measures and surgical insertion as input parameters was analyzed. The final developed model was internally validated with bootstrapping to calculate the optimism-corrected R. Frequency mismatch was minimalized for surgical insertion of 6.7 mm and insertion depth of 484°. Cochlear size clusters were derived consisting of a "small" (N = 117), "medium" (N = 171), and "large" (N = 74) cluster with mean insertion depths of 506°, 480°, and 441°, respectively. The relation between surgical insertion (LE16) and insertion depth (θE1) differed significantly between the three clusters (p < 0.01). The insertion models based on spiral fitting showed an R of 62% with mean of the residuals of -0.5 mm (SD = 1.2 mm) between the measured and predicted LE16 and a mean of 15° (SD = 83°) for θE1. Using general linear regression modeling resulted in a residual mean of -0.2 μm (SD = 0.9 mm) for measured and predicted LE16 and 0.01° (SD = 33°) for θE1. The model derived from general linear regression modeling resulted in an R of 78.7% and was validated with bootstrapping. An optimism of 0.6% was calculated using this analysis. The optimism-corrected R of 78.1% defined the estimated performance of the final insertion model in future populations. A minimal frequency mismatch for an electrode array design can be calculated to define preferable electrode array position within the cochlea. In general, to achieve a minimal frequency mismatch, the surgeon should attempt to insert the HiFocus 1 or 1J array around 6, 7, or 8 mm in case of a "small," "medium," or "large" cochlea, respectively. Development of different insertion models showed the feasibility of obtaining a surgical guidance tool to lead the surgeon during cochlear implantation depending on individual cochlear size and controllable surgical distance. The developed final insertion model predicted 78.1% of the variation in final HiFocus1 or HiFocus1J implant position.

Near-infrared autofluorescence spectroscopy of in vivo soft tissue sarcomas

Soft tissue sarcomas (STS) are a rare and heterogeneous group of malignant tumors that are often treated via surgical resection. Inadequate resection can lead to local recurrence and decreased survival rates. In this study, we investigate the hypothesis that near-infrared (NIR) autofluorescence can be utilized for tumor margin analysis by differentiating STS from the surrounding normal tissue. Intraoperative in vivo measurements were acquired from 30 patients undergoing STS resection and were characterized to differentiate between normal tissue and STS. Overall, normal muscle and fat were observed to have the highest and lowest autofluorescence intensities, respectively, with STS falling in between. With the exclusion of well-differentiated liposarcomas, the algorithm's accuracy for classifying muscle, fat, and STS was 93%, 92%, and 88%, respectively. These findings suggest that NIR autofluorescence spectroscopy has potential as a rapid and nondestructive surgical guidance tool that can inform surgeons of suspicious margins in need of immediate re-excision.

Needle optical coherence elastography for the measurement of microscale mechanical contrast deep within human breast tissues

Optical coherence elastography (OCE) is an emerging imaging technique that probes microscale mechanical contrast in tissues with the potential to differentiate healthy and malignant tissues. However, conventional OCE techniques are limited to imaging the first 1 to 2 mm of tissue in depth. We demonstrate, for the first time, OCE measurements deep within human tissues using needle OCE, extending the potential of OCE as a surgical guidance tool. We use needle OCE to detect tissue interfaces based on mechanical contrast in both normal and malignant breast tissues in freshly excised human mastectomy samples, as validated against histopathology. Further, we demonstrate the feasibility of in situ measurements >4 cm from the tissue surface using ultrasound guidance of the OCE needle probe. With further refinement, our method may potentially aid in accurate detection of the boundary of the tumor to help ensure full removal of all malignant tissues, which is critical to the success of breast-conserving surgery.

Improved assessment and treatment of abdominal aortic aneurysms: the use of 3D reconstructions as a surgical guidance tool in endovascular repair

Endovascular repair is fast becoming the treatment of choice for abdominal aortic aneurysms in anatomically suitable patients. 3D reconstructions not only aid conventional 2D measurements but also allow further analyses of the vessel anatomy. Computed tomography scan data for four male patients awaiting endovascular repair were obtained. 3D reconstructions were performed to determine measurements. Wall stress was determined on one particular case using finite element analysis. 3D reconstruction allows measurements to be obtained that can be difficult to determine using 2D images. This method complements traditional 2D approaches. Reconstructions also provided imaging of potential anatomical problems. Wall stress results showed key regions that may be possible rupture sites. 3D reconstructions greatly aid surgical planning. As stent-graft devices evolve, anatomical difficulties previously considered contraindications to endovascular repair can now be overcome with careful planning. 3D reconstruction is a useful adjunct to assessment and planning of endovascular repair.

Intraoperative Magnetic Resonance Imaging-guided neurosurgery at 3-T

Between 1997 and 2004, more than 700 neurosurgical procedures were performed in a 1.5-T magnetic resonance-guided therapy suite. During this period, the concept of high-field intraoperative magnetic resonance imaging (MRI) was validated, as was a new surgical guidance tool, the Navigus (Image-guided Neurologics, Melbourne, FL), and its methodology, prospective stereotaxy. Clinical protocols were refined to optimize surgical techniques. That implementation, the "Minnesota suite," has recently been revised, and a new suite with a 3-T MRI scanner has been developed. On the basis of experience at the initial 1.5-T suite, a new suite was designed to house a 3-T MRI scanner with wide surgical access at the rear of the scanner (opposite the patient couch). Use of electrocautery, a fiberoptic headlamp, a power drill, and MRI-compatible neurosurgical cutlery was anticipated by inclusion of waveguides and radiofrequency filter panels that penetrate the MRI suite's radiofrequency shield. An MRI-compatible head holder was adapted for use on the scanner table. A few items exhibiting limited ferromagnetism were used within the magnetic field, taking strict precautions. During the initial procedures (all magnetic resonance-guided neurobiopsies), the new suite functioned as anticipated. Although metallic artifact related to titanium needles is more challenging at 3 T than at 1.5 T, it can be contained even at 3 T. Similar to 1.5 T, such artifact is best contained when the device is oriented along B0, the main magnetic field. Surgical needles, disposable scalpels, and disposable razors, despite being minimally ferromagnetic, were easily controlled by the surgeon. An intraoperative magnetic resonance-guided neurosurgical theater has been developed with a 3-T MRI scanner. Intraoperative imaging is feasible at this field strength, and concerns regarding specific absorption rate can be allayed. Infection control procedures can be designed to permit neurosurgery within this environment. Despite the increase in magnetic field strength, safety can be maintained.