Evaluation of a novel “gross room” device aiming to increase lymph node yield in colorectal cancer specimens: Preliminary results

Background:

Colorectal cancer is the second most common cause of cancer-related death in the US. Staging is crucial to assess prognosis and treatment options. According to AJCC guidelines, at least 12 lymph nodes are required for nodal staging. However, previous studies showed the importance of retrieving as many lymph nodes as possible. Herein, we evaluated a novel, optical imaging-based device using infrared light a.k.a. CisionVision (Cision Vision, Mountain View, CA; Fig. 1) to increase lymph node yield in colorectal cancer specimens.

Design:

The CisionVision device has increased the lymph node yield significantly in all categories except low-anterior resection (Tab. 1). This result is likely due to a small number of subjects. The increase in lymph node yield was significant when all subjects were included in the analysis (average increase of 53%). The size of the lymph nodes was compared in each case separately, also categorically. This increase was particularly notable for smaller lymph nodes (<3 mm; Fig 2). In 19 cases, lymph nodes found by the device were significantly smaller, however in three cases, there was no significant difference. In the entire study, a total of 21 metastatic lymph nodes were harvested from 7 nodal positive cases; 20 by conventional grossing and 1 by CisionVision device where a patient was upstaged from T1 N1a M0 to T1 N1b M0.

Results:

The CisionVision device has increased the lymph node yield significantly in all categories except low-anterior resection (Tab. 1). This result is likely due to a small number of subjects. The increase in lymph node yield was significant when all subjects were included in the analysis (average increase of 53%). The size of the lymph nodes was compared in each case separately, also categorically. This increase was particularly notable for smaller lymph nodes (<3 mm; Fig 2). In 19 cases, lymph nodes found by the device were significantly smaller, however in three cases, there was no significant difference. In the entire study, a total of 21 metastatic lymph nodes were harvested from 7 nodal positive cases; 20 by conventional grossing and 1 by CisionVision device where a patient was upstaged from T1 N1a M0 to T1 N1b M0.

Results Table:

Conclusion:

The CisionVision device significantly increases lymph node yield, especially for smaller nodes, leading to potential stage changes in some cases (4.5%). While further research is needed to address limitations and explore broader clinical implications, our preliminary findings highlight its potential value in colorectal cancer pathology.

Authors

Kadir Isidan, MD, MS

University of Chicago Medical Center/NorthShore University HealthSystem

Chicago, IL, United States

Hussein Alnajar, Alnajar, MD

NorthShore University HealthSystem

Chicago, IL, United States

Alicia Huber, PA (ASCP)

NorthShore University HealthSystem

Chicago, IL, United States

Zitlali Montiel-Martinez, PA (ASCP)

NorthShore University HealthSystem

Franklin Park, IL, United States

John V. Groth, MD

NorthShore University HealthSystem

Libertyville, IL, United States

Enhanced Lymph Node Detection in Pancreatic Resection Cases Using CisionVision: An Institutional Study

Background:

Accurate staging and prognosis of pancreatic adenocarcinoma rely on the precise identification of regional lymph nodes (LNs). The AJCC 8th edition classifies LNs into N1 & N2 stages based on the number of LNs involved, making LN identification critical. A smaller number of LNs carries the risk of under-staging the patient while reevaluating LNs and submitting fat fragments risks overcounting LNs and upstaging the patient. CisionVision (Cision Vision, CA) (CV) is a real-time shortwave infrared imaging device to locate lymph nodes by highlighting water content contrast (Fig. 1). This study explores the utility of CV in increasing LN detection and minimizing fat submission in pancreatic resection cases.

Design:

We prospectively enrolled 8 pancreatic resection cases (4 Whipple & 4 distal pancreatectomy) from June to September 2023. Primary grossers (PG) with varying levels of expertise identified LNs manually. Subsequently, a single secondary grosser (SG) utilized CV to extract additional LNs, and the remaining fat was submitted for evaluation (Fig. 2). The average number of LNs for manual extraction, remaining fat, intended LN cassettes, and fat cassettes were calculated. Incidental LNs found microscopically were included in PGs’ LN count.

Results:

The CisionVision device has increased the lymph node yield significantly in all categories except low-anterior resection (Tab. 1). This result is likely due to a small number of subjects. The increase in lymph node yield was significant when all subjects were included in the analysis (average increase of 53%). The size of the lymph nodes was compared in each case separately, also categorically. This increase was particularly notable for smaller lymph nodes (<3 mm; Fig 2). In 19 cases, lymph nodes found by the device were significantly smaller, however in three cases, there was no significant difference. In the entire study, a total of 21 metastatic lymph nodes were harvested from 7 nodal positive cases; 20 by conventional grossing and 1 by CisionVision device where a patient was upstaged from T1 N1a M0 to T1 N1b M0.

Results Table:

Conclusion:

In our Our experience, CV use in pancreatic resection cases demonstrated a 79% increase in LN extraction and a 66% reduction in LN detection in remaining fat. This improvement has the potential to eliminate the need for remaining fat submission, leading to reduced costs, improved grosser accuracy, and ultimately better patient outcomes by more precise staging, and tailored treatment approaches. However, we acknowledge the small sample size of the study, further large-scale validation using CV at the time of initial grossing is underway, recruiting more cases and various organ resections.

Authors

Payu Raval, MD

University of Chicago NorthShore

Des Plaines, IL, United States

John V. Groth, MD

NorthShore University HealthSystem

Libertyville, IL, United States

Hussein Alnajar, Alnajar, MD

NorthShore University HealthSystem

Chicago, IL, United States

The Effectiveness of InVision, an Optical Imaging Device, in Assisting with Lymph Node Retrieval

Abstract

This colorectal case study was part of a joint study conducted by Wisconsin Diagnostic Laboratories, Rosalind Franklin University, and Cision Vision Inc. InVision is an optical device that provides enhanced contrast between lymph nodes and surrounding adipose tissue based upon differing chemical compositions in real-time without the use of radiation or contrast media.1

Through use of Cision Vision’s innovative technology, InVision (Fig. 1), lymph node yield drastically improved. Consequently, with the increase in lymph node yield, the pN (N-regional lymph node) category of the American Joint Committee on Cancer (AJCC) Tumor, Node, Metastasis (TNM) staging system was impacted.

Introduction

Lymph node retrieval in surgically excised specimens is one of the most challenging tasks completed in anatomic pathology. It can take a prosector multiple hours to finish a single lymph node search. When such searches are inadequate and the established minimums for lymph node count are not met, re-grossing is required which prolongs turnaround time for a case. Lymph node yield is of significant clinical consequence for cancer patients. Decades of clinical evidence has shown a strong correlation between the number of lymph nodes examined and patient survival.2 Therefore, prosectors are encouraged to find all the lymph nodes in each relevant specimen regardless of the time it takes and challenges it creates. This problem has also been exacerbated by the recent advent of neoadjuvant chemotherapy which shrinks the size of lymph nodes making them more difficult to find, particularly for colorectal cancer cases.

Cision Vision’s InVision product is a novel imaging device that depicts lymph nodes in high contrast against the surrounding adipose tissue.1 This is done in real-time without the need for injections or radiation. The technology was developed at the Massachusetts Institute of Technology (MIT) by Drs. Angela Belcher and Jeremy Li. It utilizes shortwave infrared light that exploits the natural water content differences which exist between lymph nodes and fat.3 Lymph nodes are high in water content. Therefore, they absorb the shortwave infrared light and appear dark on imaging. This is in contrast to adipose tissue which has a low water content and reflects light, appearing bright on imaging. Aided by the real-time visualization of lymph nodes, a prosector can palpate and dissect the tissue directly on top of the InVision imaging platform. Therefore, the prosector’s tactile skills are reinforced by the real-time visual feedback provided by the InVision device.

In this case study, the effectiveness of the InVision device was evaluated by comparing it to the results of manual palpation from a Pathologists’ Assistant (PA) with 20 years of grossing experience. The PA manually palpated the specimen and searched for lymph nodes. The lymph nodes retrieved during this step were gathered and labeled as the first batch. The PA then went through the remaining adipose tissue scanning it with use of the InVision device to see if there were additional lymph nodes that were missed during the initial, manual palpation step. If lymph nodes were found by scanning with the InVision device, these lymph nodes were submitted as a second batch. The numbers of lymph nodes in both batches are confirmed through routine histologic examination. Comparison of the lymph node counts between the two batches provided insight into the effectiveness of the InVision device for lymph node retrieval.

Case History

A 46-year-old Caucasian male presented to his general practitioner (GP) with complaints of persistent, nonspecific pelvic pain. Family history was unremarkable for rectal cancer and no associated risk factors were reported. Subsequently, the patient was referred for MRI which revealed suspected adenocarcinoma of the rectum that was clinically staged as IVA (cT3, cN1b, cM1). The primary mass was circumferential, 2.1 cm on imaging, and located 6 cm from the anal verge with mesorectal fascia involvement (MRF+), and suspicious mesorectal and presacral lymph nodes. A solitary liver mass was also present, measuring 1.5 cm in greatest dimension. Biopsies were taken of the both the rectal and liver masses. The rectal mass biopsy revealed moderately differentiated adenocarcinoma and the liver mass biopsy revealed adenocarcinoma compatible with a rectal primary. After initial diagnosis, the patient received combination neoadjuvant therapy which consisted of FOLFIRINOX+Avastin and short course radiation over 4 consecutive days. Upon completion of the aforementioned therapy, the patient underwent a low anterior resection (Fig. 2) in conjunction with a hepatic wedge excision of segments 7 and 8.

Fig. 2 Low anterior resection.

Pathologic examination of the low anterior resection was completed via use of the Quirke method. This method of prosection allows for thorough visualization of the tumor in relation to the mesorectal/circumferential radial margin (CRM) by leaving the specimen intact within the area of the mass. This area is serially sectioned from proximal to distal at 3 to 5 mm intervals and the corresponding sections are subsequently referred to as levels. Sectioning of this case revealed a 2.5 x 1.3 x 0.3 cm centrally ulcerated, endophytic, tan mass within levels 2-5 (Fig. 3). The mass measured 0.6 cm from the distal margin, 18.5 cm from the proximal margin, 0.8 cm from the anterior mesorectal margin and extended below the peritoneal reflection with focal infiltration into the muscularis propria.

As for the lymph node search, 19 lymph nodes were identified in total, 8 via use of traditional manual palpation by the prosector and 11 via use of the InVision device. Two out of eight lymph nodes found were microscopically positive for metastatic adenocarcinoma from the manual palpation batch;
1 out of 11 nodes were microscopically positive from the batch retrieved with assistance from the InVision device.

As for the lymph node search, 19 lymph nodes were identified in total, 8 via use of traditional manual palpation by the prosector and 11 via use of the InVision device. Two out of eight lymph nodes found were microscopically positive for metastatic adenocarcinoma from the manual palpation batch;
1 out of 11 nodes were microscopically positive from the batch retrieved with assistance from the InVision device.

Due to the fact that only 8 lymph nodes were found through the traditional manual palpation method, which falls short of the established minimum of 12 stipulated by AJCC and the College of American Pathologists (CAP), this case would be subject to re-grossing.

With the assistance of InVision, the total number was increased to 19, a 137.5% increase in lymph node count, bringing it into compliance with lymph node yield requirements. More importantly, because one additional positive lymph node was found, the patient’s N category was upstaged from ypN1a to ypN1b (Fig. 4).2 The final diagnosis was residual invasive moderately differentiated adenocarcinoma of the rectum without involvement of the margins and metastatic adenocarcinoma with extensive liver necrosis, consistent with metastasis from a rectal primary. The pathologic stage was reported as ypT2 pN1b PM1a.

Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer Staging System (2020)

Fig. 4 AJCC TNM staging for colorectal carcinoma with specific information related to N categorization.

Discussion

Colorectal cancer staging utilizes the TNM system established by AJCC. Pre-fix “p” designates pathologic stage while “c” denotes clinical stage. Cases staged subsequent to use of neoadjuvant therapy utilize the pre-fix “yp”. These designations are important for QA/QC purposes across professions. As with any cancer, as the stage increases, patient prognosis inevitably decreases.

A minimum number of regional nodes is needed for accurate N category staging and is recommended by the National Comprehensive Cancer Network (NCCN) and accepted by the AJCC and CAP (Fig. 4).4 The minimum number of lymph nodes determined to be adequate for accurate colorectal cancer staging is 12. For reasons unknown, an association has been found between examination of 12 or more lymph nodes and improved patient survival.4

Additionally, as outlined in the Intergroup Trial INT – 0089, conducted by Le Voyer TE, Sigurdson ER, Hanlon AL, et al., an increase in the number of lymph nodes examined correlated with an increase in survival in patients with node negative and node positive disease.5 These findings highlight the importance of lymph node yield for accurate N category staging and predictions related to patient survival.

Use of the novel InVision device, in this instance, upstaged the patient from ypN1a to ypN1b and improved lymph node yield by 137.5%. By doing so, correlation within the N category between clinical and pathologic staging was achieved. In this particular case, the minor staging change does not alter the patient’s treatment regimen. However, it is reasonable to assume that there might be instances where InVision can potentially assist prosectors in finding positive lymph nodes that could have been missed through use of manual palpation techniques alone; therefore, rendering consequential changes to staging and treatment options. Larger studies need to be completed to have a more thorough and accurate assessment of the effectiveness of InVision.

Conclusion:

Use of InVision improved lymph node retrieval by allowing the institution to meet the NCCN recommendation. It also impacted staging within the N category and decreased turnaround time through elimination of the need for re-grossing. While this is a single example of the value the innovative device provided, larger studies are being conducted to determine the impact on patient care and subsequent treatment decisions.

Authors

Mary L. Mattes, MS, PA(ASCP)CM

Rosalind Franklin University

Chicago, IL, United States

Dennis Strenk, PA(ASCP)CM

Wisconsin Diagnostic Laboratories

Milwaukee, WI, United States

Jeremy Li, PhD

Cision Vision Inc.

Mountain View, CA, United States

References

  1. Cision Vision Inc. https://cisionvision.com. Accessed May 2023.
  2. Amin MB, Edge SB, Greene FL, et al. AJCC Cancer Staging Manual 8th ed. Springer, 2018. Print.
  3. Li, Z., Huang, S., He, Y., et al. bioRxiv 2023.01.13.523938; doi: https://doi org/10.1101/2023.01.13.523938.
  4. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology – Colon Cancer. Version 3.2022.
    https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed March 2023.
  5. Le Voyer TE, Sigurdson ER, Hanlon AL, et al. Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089. J Clin Oncol 2003;21:29122919. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12885809.

Shortwave infrared imaging increases the number of lymph nodes and the number of positive lymph nodes in surgical pathology specimens: – a 104-patient study

Introduction

Adequate lymph node staging is critically important for accurate cancer staging.1 It has been widely shown that the number of lymph nodes examined is correlated with overall improved prognosis, possibly because of increased accuracy in staging. This association has been reported in colon cancer,1 rectal cancer,2 gastric cancer,3 lung cancer,4 head and neck cancers,5 among others. As a result, different minimum numbers of lymph nodes have been proposed across many cancer types. The most well-known benchmark is a yield of at least 12 lymph nodes for colorectal cancer specimens.6

The task of finding lymph nodes is laborious, time-consuming, and produces inconsistent results.7-9 This problem has even become a common point of friction between pathology and surgery departments.10

Attempts have been made to improve the efficiency and accuracy of lymph node dissection over the past few decades. The most notable solution is a method in which the specimen is soaked in organic solvents, such as acetone,11 Carnoy’s solution,12 and GEWF solution.13 However, this procedure significantly extends turnaround time and requires a designated chemical handling protocol. As a result, it has not been adopted in many institutions for routine gross examination. Another alternative is to submit the specimens in entireties. This can be done for smaller specimens,14 but is not feasible for large cases. Even for small cases, it is an inefficient and wasteful process that results in processing greater numbers of cassettes and increased microscopic review time.14

Shortwave infrared (1000 – 2000 nm) imaging is a novel emerging field for pathological imaging. The unique property of this wavelength range is that water, while being transparent in the visible light (400 – 700 nm) and near-infrared (700 – 1000 nm) range, is highly absorbent of shortwave infrared light. Therefore, when shortwave infrared light is illuminated onto biological tissues, the tissue types that are rich in water, such as lymph node and lymphatic vessels, will absorb the light and appear as dark areas. The tissue types that are low in water content, such as fat, will reflect the shortwave infrared light and appear as bright areas.

Cision InVision™ is an imaging device based on shortwave infrared imaging. Surgical specimens can be placed on the glass window of the imaging device and a reflection-based shortwave infrared image will be displayed on its monitor in real time. (Figure 1A)

Figure. 1
(A) A prosector using the Cision InVision™ shortwave infrared imaging device on a surgical resection specimen for lymph node dissection. (B) Example case (Case H1-2) from a breast cancer axillary lymph node dissection in which the only positive lymph node was identified via shortwave infrared imaging. Metastatic carcinoma is located within lymph node parenchyma (circle) (B: H&E, 4X), and consists of cohesive cells with large, pleomorphic nuclei, prominent nucleoli, and readily identifiable mitoses (arrow) (C: H&E, 20X).

The prosector can manually palpate the surgical specimen and dissect out the lymph node candidates on the glass window. It is worth noting that the technique only displays a reflection image of shortwave infrared light highlighting the natural water content difference – it does not specifically highlight the lymph nodes for the prosectors. The prosector still needs to rely on one’s prior experience with lymph node grossing to determine whether the identified darker areas are lymph nodes, as opposed to vessels, or other structures that may display high relative water content. The purpose of this pilot study was to investigate the effectiveness of this novel imaging technology to improve lymph node yield and its impact on cancer staging.

Methods

Patients

This is a pilot study where the effectiveness of shortwave infrared imaging for lymph node searches is evaluated for the first time. The study included 104 cancer patients from two hospitals, 37 cases from an academic hospital and 67 cases from a large community hospital. The cancer types for these cases include colon (68 cases), rectum (17 cases), breast (3 cases), pancreas (8 cases), stomach (5 cases), skin (1 case) and small bowel (2 cases).

Methods

Pathologists and Pathologists’ Assistants

The gross examination procedures and the operation of the shortwave infrared imaging device were conducted by pathologists and board-certified Pathologists’ Assistants (PA) under the supervision of board-certified pathologists. Microscopic examinations of submitted lymph node candidates were confirmed by board certified pathologists.

Methods

Study Procedure

To evaluate the effectiveness of shortwave infrared imaging in assisting lymph node searches compared to standard of care, the study is designed to have two steps:

In the first step, the gross examination for lymph nodes was performed with visual inspection and manual palpation. The lymph node candidates retrieved in this step were placed in the first batch of cassettes, Batch A. This step is representative of the current standard of care.

In the second step, the same PA, under the supervision of a pathologist, used the Cision InVision™ Pathology Imaging System to search for additional lymph nodes in residual specimens after the first step. The lymph node candidates that were retrieved in this step were placed in the second batch of cassettes, Batch B.

Batch A and B cassettes were processed via standard histological protocols. Microscopic review was performed by board-certified pathologists to confirm the total numbers of lymph nodes and the numbers of positive lymph nodes in Batches A and B.

Methods

Statistics

Poisson regression was used to test the hypotheses that 1 the number of lymph nodes identified by shortwave infrared imaging was significantly different than zero,2 the number of positive lymph nodes identified by shortwave infrared imaging was significantly different than zero.

This statistical technique was used to test hypotheses where the outcome scale was counted data. The two hypothesis outcomes comprised distinct counts of total lymph nodes detected, and distinct counts of positive lymph nodes detected. Statistical significance was concluded with Wald Chi Square p values less than 0.05. Analysis was run using the GENMOD procedure in SAS 9.4 (Cary, NC), with the Poisson distribution and the log-linear regression model specifications.

Results

Table 1. Total lymph node and positive lymph node counts with traditional palpation and with assistance via shortwave infrared imaging in Hospital 1 (H1)
Table 2.
Total lymph node and positive lymph node counts with traditional palpation and with assistance via shortwave infrared imaging in Hospital 2 (H2)

Improvement in lymph node counts

As shown in Table 3, gross examination assisted by shortwave infrared imaging identified a significant number (nonzero) of lymph nodes in residual tissue after standard of care lymph node dissection.
b = 1.57, X 2= 1232.79, p < 0.0001.

Table 3.
Comparison of nodal yield with traditional palpation and with shortwave infrared imaging

As shown in Table 4, in 36 of the 37 cases (97.3%) in Hospital 1 and 54 of the 67 cases (80.6%) in Hospital 2, additional lymph nodes were identified with the assistance of shortwave infrared imaging. Overall, in 90 of the 104 cases (86.5%), additional lymph nodes were identified with the assistance of shortwave infrared imaging.

Table 4.
Comparison of hospital 1 and hospital 2

Improvement in positive lymph node counts

As shown in Table 3, gross examination assisted by shortwave infrared imaging identified a significant number (nonzero) of positive lymph nodes in samples discarded after standard of care lymph node dissection, b = -2.01, X 2= 56.30, p < 0.0001.

As shown in Table 4, in 4 of the 37 cases (10.8%) in Hospital 1 and 7 of the 67 cases (10.4%) in Hospital 2, additional positive lymph nodes were identified with the assistance of shortwave infrared imaging. Overall, in 11 of the 104 cases (10.6%), additional lymph nodes were identified with the assistance of shortwave infrared imaging.

There were 31 lymph node positive cases in total (8 from Hospital 1 and 23 from Hospital 2). In 4 of these positive cases (12.9%), the positive lymph nodes were only discovered by shortwave infrared imaging, with no positive lymph nodes being identified through the standard of care visual and manual dissection. These 4 positive cases would have been wrongly staged as lymph node negative in the absence of shortwave infrared imaging support. An example where the only positive lymph node was identified with the help of shortwave infrared imaging was depicted in Figure 1(B) and (C).

Also, in 11 of the 31 the lymph node positive cases (35.5%), additional lymph nodes were identified with the assistance of shortwave infrared imaging.

DISCUSSION

The main purpose of this study was to evaluate the effectiveness of shortwave infrared imaging in 1 increasing lymph node counts and 2 identifying additional positive lymph nodes. As shown in the RESULTS section, both hypotheses were strongly supported.

In addition to supporting these two main hypotheses, we also investigated the effectiveness of shortwave infrared imaging for improving compliance of gross examination of colorectal cancer cases. Established guidelines in the United States dictate that colorectal cancer cases yield a minimum of twelve lymph nodes. Failure in reaching twelve lymph nodes after the first round of gross examination results in re-examination of residual adipose tissue, which is time-consuming, labor intensive, and economically costly.15 This problem is particularly common for cases that had been previously treated with radiation or chemotherapy.2 Lymph nodes often become smaller and are thus more challenging to retrieve after such treatments, with reassessment of the gross specimen multiple times being common for such cases. In this study, only 34.1% (29/85) of colorectal cancer cases achieved the required number of 12 lymph nodes after the first round of grossing. Shortwave infrared imaging brought 35.7% (20/56) of the non-compliant cases into compliance, obviating the need to return to the specimen in over a third of these cases.

The data provides compelling evidence for the benefit of shortwave infrared imaging in lymph node dissection in the surgical pathology laboratory. However, as a first large scale multi-center pilot study of this emerging technology, there are several limitations to this study.

The first limitation is the inconsistency in the user proficiency in the technology. When comparing the percentage improvement that resulted from the assistance of shortwave infrared imaging in 1 increasing lymph node counts, 2 increasing positive lymph node counts, and 3 improving compliance, Hospital 1 consistently showed a larger improvement, which could suggest a higher proficiency level of the users in Hospital 1. Because Cision InVision™ Pathology Imaging System does not directly identify lymph nodes (but rather shows a shortwave infrared reflection which is indicative of the natural water content difference between tissue types), the users are responsible for interpreting the images in real time and deciding on which tissue pieces to submit. Robust training and testing protocols for users in a future study can help overcome this limitation.

The second limitation is that the two-step evaluation process is not representative of the practical workflow for using the shortwave infrared imaging system. In a real-world scenario, the first round of gross examination can be carried out together with the assistance of the shortwave infrared imaging system. There is no practical reason for the user to only use the device for searching additional lymph nodes in residual adipose tissue after manual palpation is completed. One can argue that the shortwave infrared imaging system can have an even larger impact in a real-world scenario compared to what has been shown in this study, because the two-step approach places this new technology in a disadvantaged position to demonstrate its effectiveness. Future studies where shortwave infrared imaging is used in the first round of gross examination may be conducted to measure the effectiveness of this new technology in standard practice settings.

The third limitation is that this study was not completely blinded. Although we blinded the pathologists while they review histological results from different batches, there is no way to blind the prosectors with regard to gross examination with or without the device. The psychological factors of the users of the device could have played a role in affecting the numbers of lymph node counts. However, because these procedures were conducted all by experienced board-certified PAs with patients’ best interests in mind, the impact of this role is unlikely to have changed any of the major conclusions that we drew from the data above.

Other potential effects that shortwave infrared imaging can have that were not investigated in this study are 1 time saving in lymph node searches and 2 cost saving for reducing the number of cassettes submitted for histological processing. Future studies need to be conducted to evaluate these potential benefits.

In conclusion, this two-center, 104-patient large-scale pilot study, demonstrated that shortwave infrared imaging helps not only find additional lymph nodes, but also additional positive lymph nodes. Future studies will need to be conducted to overcome the limitations of this study and to investigate other potential benefits of shortwave infrared imaging.

Conclusion:

Shortwave infrared imaging increases the number of lymph nodes and the number of positive lymph nodes in surgical pathology specimens compared to traditional visual and manual dissection.

Authors

Julie Jorns, MD

Medical College of Wisconsin

Milwaukee, WI

Robert Smith, MD

St. Dominic Hospital

Jackson, MS, United States

Dennis Strenk, PA(ASCP)

Wisconsin Diagnostic Laboratories

Milwaukee, WI

Amanda Stauble, NP

St. Dominic Hospital

Jackson, MS

Ryan Seltzer, MD

Cision Vision Inc.

Mountain View, CA

John Manuel, PA(ASCP)

Cision Vision Inc.

Mountain View, CA

Matthew Rosenbaum, MD

Cision Vision Inc.

Mountain View, CA

James Almas, MD

Cision Vision Inc.

Mountain View, CA

Jeremy Li, PhD

Cision Vision Inc.

Mountain View, CA

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Shortwave Infrared Orthogonal Polarization Imaging for label-free nerve visualization: A preliminary cadaveric study

Objective

Intraoperative identification and mapping of cranial nerves remain some of the most challenging tasks in neurosurgery. Shortwave Infrared Orthogonal Polarization Imaging (SWIR-OPI) is an emerging technology that leverages significant water absorption at specific wavelengths to precisely detect and distinguish tissues with varying water content. Theoretically, nerves, which have lower water content, can be effectively distinguished from the higher water content environment of the cerebral cortex using SWIR-OPI. However, this technology has not yet been applied in any neurosurgical scenarios. This study investigates the potential application of SWIR-OPI in neurosurgery by examining its real-time imaging capabilities in fresh human and sheep cadaveric specimens.

Methods

SWIR-OPI images were collected from ten fresh, unembalmed human cadaveric specimens and five fresh sheep specimens. Anatomical landmarks, including cranial nerves, neural fibers, and cerebral cortex, were systematically evaluated. The Weber Contrast coefficient was employed to quantitatively analyze and compare the visibility of these structures within different environments.

Results

An exoscopy system equipped with SWIR-OPI, integrating high-performance SWIR light sources, linear polarizers, SWIR lenses, and InGaAs cameras, has been successfully established (Figure 1A). Analysis of SWIR-OPI images from cross-sectional sheep brains demonstrated that the 1550 nm wavelength exhibited the highest specificity for white matter tissues, with a significantly higher Weber Contrast coefficient compared to other short wavelengths (p<0.01, Figure 1B, C). Under 1550 nm SWIR-OPI, cranial nerves and fiber bundles (white matter) appeared as high-signal (white) regions due to their lower water content, while the cerebral cortex and nuclei (gray matter), with higher water content, appeared as low-signal (black) regions. The application of SWIR-OPI in cadaveric human heads revealed distinct and consistent patterns of high Weber Contrast coefficients in cranial nerves and fiber bundles compared to visible light imaging (p<0.01, Figure 1D, E). On the surface and cross-sections of the brainstem, SWIR-OPI images identified nuclei and gray matter contours that were indiscernible with standard visible light (Figure 1F-I).

Figure. 1
Exoscopy equipped with SWIR-OPI for nerve visualization on sheep and human specimen, revealing distinct and consistent high signals in cranial nerves and fiber bundles.

Conclusion:

SWIR-OPI provides clear, label-free, and real-time visualization of cranial nerves and fibers within surrounding cerebral structures, demonstrating significant potential for precise intraoperative nerve identification and mapping.

Authors

Yuanzhi Xu, MD

Stanford Hospital

Palo Alto, CA

Jeremy Li, PhD

Cision Vision

Mountain View, CA

Abdullah Shahid

Cision Vision

Mountain View, CA

Vera Vigo, MD

Stanford Hospital

Palo Alto, CA

Juan Fernandez-Miranda, MD

Stanford Hospital

Palo Alto, CA

Shortwave Infrared Orthogonal Polarization Imaging for label-free nerve visualization: A preliminary cadaveric study

Objective

Intraoperative identification and mapping of cranial nerves remain some of the most challenging tasks in neurosurgery. Shortwave Infrared Orthogonal Polarization Imaging (SWIR-OPI) is an emerging technology that leverages significant water absorption at specific wavelengths to precisely detect and distinguish tissues with varying water content. Theoretically, nerves, which have lower water content, can be effectively distinguished from the higher water content environment of the cerebral cortex using SWIR-OPI. However, this technology has not yet been applied in any neurosurgical scenarios. This study investigates the potential application of SWIR-OPI in neurosurgery by examining its real-time imaging capabilities in fresh human and sheep cadaveric specimens.

Methods

SWIR-OPI images were collected from ten fresh, unembalmed human cadaveric specimens and five fresh sheep specimens. Anatomical landmarks, including cranial nerves, neural fibers, and cerebral cortex, were systematically evaluated. The Weber Contrast coefficient was employed to quantitatively analyze and compare the visibility of these structures within different environments.

Results

An exoscopy system equipped with SWIR-OPI, integrating high-performance SWIR light sources, linear polarizers, SWIR lenses, and InGaAs cameras, has been successfully established (Figure 1A). Analysis of SWIR-OPI images from cross-sectional sheep brains demonstrated that the 1550 nm wavelength exhibited the highest specificity for white matter tissues, with a significantly higher Weber Contrast coefficient compared to other short wavelengths (p<0.01, Figure 1B, C). Under 1550 nm SWIR-OPI, cranial nerves and fiber bundles (white matter) appeared as high-signal (white) regions due to their lower water content, while the cerebral cortex and nuclei (gray matter), with higher water content, appeared as low-signal (black) regions. The application of SWIR-OPI in cadaveric human heads revealed distinct and consistent patterns of high Weber Contrast coefficients in cranial nerves and fiber bundles compared to visible light imaging (p<0.01, Figure 1D, E). On the surface and cross-sections of the brainstem, SWIR-OPI images identified nuclei and gray matter contours that were indiscernible with standard visible light (Figure 1F-I).

Figure. 1
Exoscopy equipped with SWIR-OPI for nerve visualization on sheep and human specimen, revealing distinct and consistent high signals in cranial nerves and fiber bundles.

Conclusion:

SWIR-OPI provides clear, label-free, and real-time visualization of cranial nerves and fibers within surrounding cerebral structures, demonstrating significant potential for precise intraoperative nerve identification and mapping.

Authors

Yuanzhi Xu, MD

Stanford Hospital

Palo Alto, CA

Jeremy Li, PhD

Cision Vision

Mountain View, CA

Abdullah Shahid

Cision Vision

Mountain View, CA

Vera Vigo, MD

Stanford Hospital

Palo Alto, CA

Juan Fernandez-Miranda, MD

Stanford Hospital

Palo Alto, CA

The Use of InVision as a New Modality for Lymph Node Dissection to Standardize Variability without Sacrificing Patient Care

Abstract

Lymph node dissection is an important step in grossing, in which findings go on to affect patient prognosis and care management. The standard technique for finding lymph nodes is through manual palpation – an expertise that usually takes years to gain. The only way to improve on such skills is through practicing through the real clinical cases, where patient care is on the line. This could present potential possibilities for less-than-optimal patient outcomes. Fixatives, such as Dissect Aid and Carnoy’s solutions, are sometimes used to help address this issue. But they significantly increase the overall turnaround time, expose prosectors to potential health hazards, while still only marginally mitigate the issue. In this abstract, we introduce the InVision, a new optical imager for gross examination produced by Cision Vision, as a new modality that will aid finding lymph nodes and gaining experience for newer and inexperienced prosectors, without sacrificing patient care. Its real-time imaging capability also removes the need for chemical fixative – shortening the turnaround time and eliminating exposure to health hazard.

Background

Lymph node status and yield are major indicators in prognostication and cancer care management. The N-stage and number of metastatic lymph nodes yielded during grossing go on to define patient treatment and suggest patient prognosis. Although there are lymph node minimums in certain tumor types, literature1 suggests that finding lymph nodes in excess of these minimums provides higher quality patient care. Generally speaking, a higher yield of lymph nodes provides more confident insight to lymph node staging and thus avoiding understaging and its consequence of withholding vital treatment for the patient.

Literature2 suggests that inconsistencies in lymph node yields can be found at the hospital level. Prosectors of lymph node dissection range from pathologists,  Pathologists’ Assistant, or the residents. Gaining expertise and skill in the difficult craft of lymph node searches through manual palpation requires practice in caseloads. This means that inexperienced prosectors must begin their practice on real patient specimens.

While the learning-through-doing approach is generally true for medical practitioners throughout different specialties and tasks, lymph node searches through manual palpation is unique in three different aspects – (1) it is extremely clinically consequential, (2) it is extremely technically challenging, and (3) mistakes are not detectable due to intrinsic variabilities across individual specimens.

While there is not a defined expectation of efficiency for newer prosectors, time is a valuable and finite resource, especially since most gross rooms are severely understaffed. The time pressure to fulfill considerate amount of workload responsibilities while gaining experience at the same time means patient care can potentially be comprised along the way.

Current alternatives exist but are limited to chemical aids, of which available options are limited to irritants and carcinogens, and all require additional fixation. Non-chemical aids currently do not exist as a standard of care.

InVision is based on a new optical imaging modality invented by Cision Vision. It uses ex-military technologies that were previously inaccessible to civil applications. The fundamental mechanism is that InVision uses shortwave infrared light that lets the natural water content contrast between fat and lymph nodes manifest itself in real time without any injection or radiation. Most importantly, it does not replace the manual palpation, but rather enhance it by providing an additional dimension of information – real time visual feedback. In the context of prosector education, the tactile feeling memory of lymph nodes through manual palpation can be reinforced by the visual feedback – therefore potentially shortening the learning curve for gaining expertise in lymph node searches.

Methodology

The prosectors begin lymph node dissection by sectioning and removing fat or other soft tissue with suspected lymph node candidates, and place against the screen of the device. With the tissue of interest on the functional platform, the prosector manually palpates for lymph nodes, and/or sections the tissue to reveal lymph node candidates. While the prosector grosses for lymph nodes against the platform, the device screen reveals a contrasted image that highlights lymphoid tissue against non-lymphoid tissue. Lymphoid tissue appears as a darker structure, while fatty tissue appears as lighter-to-translucent structures. The prosector combines the manual palpation and/or sectioning with the visual contrast provided by the device to more quickly acknowledge and submit lymph nodes for histopathology.

As a proof-of-concept study, subjective interviews were carried out to assess the usability and the potential educational value of the InVision product. Users with different experienced levels, from PA students, residents, pathologists and extremely experienced PAs, were interviewed and surveyed.

Figure. 1
InVision’s workflow in a grossing bench

Results

The interviewees expressed unanimous positive responses to the usability of the InVision product. Quotes include:

“That’s amazing. The amount of Friday nights in residency that could have been save by this are ridiculous” – Pathologist.

“I love this idea — something that we had been dreaming of as residents.” – Pathologist

“I became a neuropathologist because there wasn’t something like this when I was a resident years ago.” – Pathologist

“This device definitely makes finding lymph nodes a lot easier and it gives you the confidence that there is no lymph node left in the residual fat tissue even after the first round of gross.” – Resident

“This definitely helped me find lymph nodes that I could have missed.” – PA with 20+ years of grossing experience

“This makes finding lymph nodes far less intimidating. It also makes the process far less tedious too.” – new PA with minimal experience

Figure. 2
Lymph node network in the mesentery specimen
Figure. 3
Lymph node network in head and neck specimen
Figure. 4
Large and minute lymph nodes in head and neck specimen

Conclusion:

Lymph node yield is paramount to patient care and prognosis, and may be affected in a learning setting with newer prosectors. The InVision device introduces a new modality to lymph node dissection and can be a valuable tool in reinforcing confidence and experience, without sacrificing patient care. 

Authors

Anh Tran, PA (ASCP)

Cision Vision

Mountain View, CA

Jeremy Li, PhD

Cision Vision

Mountain View, CA