Shear wave velocity measurements obtained in different regions are repeatable for presumed normal canine lymph nodes: A pilot study.

Shear wave elastography (SWE) has been applied as a noninvasive method for predicting regional lymph node (LN) metastases in human and veterinary patients. However, published studies describing standardized protocols and repeatability of this technique are currently lacking. The objective of this prospective, pilot, observer agreement study was to determine whether different shear wave velocity (SWV) measurements obtained in different regions of presumed normal canine LNs would be repeatable. Two imagers consecutively performed shear wave elastography of submandibular, superficial inguinal, and popliteal LNs in 10, clinically healthy adult dogs. Ten elastograms of each LN were acquired by each imager. In each adequate elastogram, three regions of interest (ROIs) were placed in the softest and stiffest region of the LN. Additionally, one ROI was drawn covering the entire LN. In each ROI, mean, median, and maximum SWVs were calculated. Mean values for the mean, median, and maximum SWVs varied from 2.33 to 3.10 m/s, 2.32 to 3.10 m/s, and 2.61 to 4.09 m/s, respectively. Intra- and interobserver agreements were acceptable. Superficial inguinal LNs demonstrated the highest intra- and interobserver agreement, followed by the popliteal and the submandibular LNs, respectively. Using the different measurements (mean, median, or maximum SWVs) had no significant effect on the intra- and interobserver variability, neither did the region (softest, stiffest, or entire LN). Findings indicated that all evaluated measurements and regions could be used to obtain reliable elastography data of presumed normal canine LNs. Clinical trials in dogs with cancer are necessary to compare SWVs of metastatic LNs with the reported SWVs and evaluate whether various measurements and regions can also be used in metastatic LNs.

Shear wave elastography of lymph nodes in dogs with head and neck cancer: A pilot study.

Shear wave elastography (SWE) is a novel ultrasound imaging technique, used in human medicine to differentiate metastatic from non-metastatic lymph nodes (LNs) based on higher tissue stiffness. The objective of this pilot study was to evaluate whether canine metastatic LNs were stiffer compared to non-metastatic LNs. SWE of sentinel or regional LNs in dogs with head and neck cancer was performed. Ten elastograms of each LN were acquired. In each elastogram, mean, median, and maximum shear wave velocities (SWVs) were calculated in the most elastic region, the stiffest region, and the entire LN. The means of those SWVs for each region of each LN were subsequently calculated. Furthermore, a stepwise subsampling was performed to assess the effect of the number of acquired elastograms on the consistency of the classification of a LN as metastatic or not. Twenty-four LNs in 15 dogs with head and neck cancer were included, of which 10 LNs were metastatic. Metastatic medial retropharyngeal and mandibular LNs were successfully distinguished from non-metastatic LNs based on higher mean and median SWVs in the stiffest region and higher maximum SWVs in entire LNs. Furthermore, maximum SWVs in the stiffest region of mandibular LNs were higher in metastatic LNs compared to non-metastatic LNs. Downstream analyses demonstrated that at least eight elastograms were necessary to perform reliable analyses. This pilot trial demonstrated that SWE has potential to discriminate metastatic from non-metastatic LNs; however, LN status should be based on at least eight elastograms in future clinical trials.

Intra- and Inter-Observer Variability of Quantitative Parameters Used in Contrast-Enhanced Ultrasound of Kidneys of Healthy Cats.

Contrast-enhanced ultrasound (CEUS) is a non-invasive imaging technique which allows qualitative and quantitative assessment of tissue perfusion. Although CEUS offers numerous advantages, a major challenge remains the variability in tissue perfusion quantification. This study aimed to assess intra- and inter-observer variability for quantification of renal perfusion. Two observers with different levels of expertise performed a quantitative analysis of 36 renal CEUS studies, twice. The CEUS data were collected from 12 healthy cats at 3 different time points with a 7-day interval. The inter- and intra-observer agreement was assessed by the intraclass correlation coefficient. Within and between observers, a good agreement was demonstrated for intensity-related parameters in the cortex, medulla, and interlobular artery. For some parameters, ICCinter was considerably lower than ICCintra, mostly when the ROI encompassed the entire kidney or medulla. With the exception of time to peak (TTP) and mean transit time (mTTI), time-related and slope-related parameters showed poor agreement among observers. In conclusion, it may be advised against having the quantitative assessment of renal perfusion performed by different observers, especially if their experience levels differ. The cortical mTTI seemed to be the most appropriate parameter as it showed a favorable inter-observer agreement and inter-period agreement.

Fluorescence-guided surgery using indocyanine green in dogs with superficial solid tumours.

BACKGROUND: Near-infrared fluorescence (NIRF) imaging is a relatively novel technique that can aid surgeons during intraoperative tumour identification. METHODS: Nine canine oncology patients (five mammary gland tumours, three mast cell tumours and one melanoma) received intravenous indocyanine green (ICG). After 24 hours, tumours were resected and fluorescence intensities of tumours and surroundings were evaluated. Additional wound bed tissue was resected if residual fluorescence was present after tumour resection. Ex vivo, fluorescence-guided dissection was performed to separate tumour from surrounding tissue. RESULTS: Intraoperative NIRF-guided tumour delineation was feasible in four out of nine dogs. Wound bed imaging after tumour removal identified nine additional fluorescent lesions, of which four contained tumour tissue. One of these four true positive in vivo lesions was missed by standard-of-care inspection. Ex vivo fluorescence-guided tumour dissection showed a sensitivity of 72 per cent and a specificity of 80 per cent in discriminating between tumour and surrounding tissue. CONCLUSION: The value of ICG for intraoperative tumour delineation seems more limited than originally thought. Although NIRF imaging using ICG did identify remaining tumour tissue in the wound bed, a high false positive rate was also observed.

Preliminary safety and imaging efficacy of the near-infrared fluorescent contrast agent DA364 during fluorescence-guided surgery in dogs with spontaneous superficial tumors.

Tumor-targeting contrast agents may facilitate resection of solid neoplasms during fluorescence-guided surgery. Preliminary safety and imaging efficacy of the near-infrared fluorescent probe DA364 were evaluated during surgical resection of spontaneous solid tumors in 24 dogs. Intra-operative imaging was performed in situ and on excised specimens to evaluate fluorescence intensities of tumor and adjacent tissues. After standard-of-care tumor resection, the wound bed was imaged again, and additional tissue was excised if residual fluorescence was detected. DA364 was well tolerated after intravenous administration. The median tumor-to-background ratio in situ for mammary tumors, mast cell tumors and sarcomas was 1.8 (range 1.2-3.9), 2.2 (range 1.0-5.6), and 4.2 (range 2.0-4.3), respectively. Qualitative intra-operative tumor identification was feasible in half of the cases. Remaining fluorescence was detected in four wound beds that contained residual disease, and in11 tumor-free wound beds, confirmed by histopathology. Overall, DA364 did not raise safety concerns and showed accumulation in different types of spontaneous tumors, showing potential to pinpoint residual disease. Larger clinical trials are necessary to select accurate dosing and imaging protocols for specific indications to evaluate the sensitivity and specificity of the agent.

Sentinel lymph node mapping by near-infrared fluorescence imaging and contrast-enhanced ultrasound in healthy dogs.

Sentinel lymph node (SLN) mapping is a valuable and crucial diagnostic procedure in staging malignancies. We compared two non-invasive techniques, near-infrared (NIR) fluorescence imaging and contrast-enhanced ultrasound (CEUS), to identify the SLNs in three superficial anatomical regions in an animal model. Six healthy laboratory dogs were included in a proof-of-concept trial. A NIR fluorescent dye (Indocyanine Green) and microbubbles (Sonovue) were consecutively injected subdermally in the Inguinal, axillary and popliteal region to map the SLNs. Transcutaneous NIR fluorescence imaging identified SLNs in 17 out of a total of 18 occasions. CEUS identified SLNs in all regions (18/18). Whereas NIR fluorescence imaging performed better in the visualization of the afferent lymphatic tract, CEUS demonstrated different filling patterns of the SLNs, a feature potentially critical for the concept of SLN mapping in cancer patients. Both NIR fluorescence imaging and CEUS are safe, non-invasive, practical and accurate methods to perform real-time transcutaneous SLN mapping with potential in a clinical setting.

Clinical use of organic near-infrared fluorescent contrast agents in image-guided oncologic procedures and its potential in veterinary oncology.

One of the major challenges in surgical oncology is the intraoperative discrimination of tumoural versus healthy tissue. Until today, surgeons rely on visual inspection and palpation to define the tumoural margins during surgery and, unfortunately, for various cancer types, the local recurrence rate thus remains unacceptably high. Near-infrared (NIR) fluorescence imaging is an optical imaging technique that can provide real-time preoperative and intraoperative information after administration of a fluorescent probe that emits NIR light once exposed to a NIR light source. This technique is safe, cost-effective and technically easy. Several NIR fluorescent probes are currently studied for their ability to highlight neoplastic cells. In addition, NIR fluorescence imaging holds great promise for sentinel lymph node mapping. The aim of this manuscript is to provide a literature review of the current organic NIR fluorescent probes tested in the light of human oncology and to introduce fluorescence imaging as a valuable asset in veterinary oncology.