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At least 19 records

Future Liver Remnant Indocyanine Green Plasma Clearance Rate as a Predictor of Post-hepatectomy Liver Failure After Portal Vein Embolization

PurposeTo evaluate the utility of future liver remnant plasma clearance rate of indocyanine green (ICGK-F) for predicting post-hepatectomy liver failure (PHLF) compared with percentage future liver remnant volume-to-total liver volume ratio (%FLR) after portal vein embolization (PVE).Materials and MethodsPVE procedures in 20 patients (15 patients underwent PVE with absolute ethanol; 5 patients with gelatin particles) from 2010 to 2017 were analyzed. %FLR = future liver remnant volume (ml)/[total liver volume (ml) − tumor volume (ml)] × 100; ICGK-F = plasma clearance rate of indocyanine green (ICGK) × %FLR/100 were calculated before and after PVE. PHLF was categorized according to the criteria of the International Study Group of Liver Surgery. For predicting PHLF, we compared the ICGK-F and %FLR after PVE between the grade A PHLF group and the non-grade A PHLF (grades B and C) group.ResultsAll PVE procedures were successful. While the ICGK-F of the grade A PHLF group (median 0.073, n = 16) was about twice that of the non-grade A PHLF group (median 0.043, n = 4), showing a significant difference (Mann–Whitney U test: P = 0.002), there was no significant difference in %FLR between the grade A PHLF group and the non-grade A PHLF group (Mann–Whitney U test: P = 0.335).ConclusionICGK-F was significantly higher in the grade A PHLF group than in the non-grade A PHLF group (grades B and C), and ICGK-F was more useful for predicting PHLF than %FLR.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Indocyanine Green Fluorescence Imaging with Lymphoscintigraphy for Sentinel Node Biopsy in Melanoma: Increasing the Sentinel Lymph Node-Positive Rate

Introduction: The goal of this study was to analyze patients who underwent a sentinel lymph node biopsy (SLNB) in melanoma with the combination of radioisotope lymphoscintigraphy and indocyanine green (ICG) fluorescence imaging to compare our true positive (TP) rate, a means to perform immediate analysis of the SLNB, with that of the literature. Methods: Consecutive cutaneous melanoma patients who underwent SLNB with lymphoscintigraphy and ICG-based fluorescence imaging by the senior author (BG) from 2012 to 2018 were prospectively enrolled. The average expected SLN-positive rate per T stage was calculated based on three studies and compared with our SLN-positive rate. Results: Overall, 574 consecutive patients were analyzed. Average Breslow thickness was 1.9 mm. A total of 1754 sentinel nodes were sampled; 1497 were identified by gamma probe signaling and ICG, 241 were identified by gamma probe signaling only, and 16 were identified by ICG only. There were 123 (21.4%) patients with at least one positive SLN; 113 (91.9%) had at least one positive node identified with both gamma probe signaling and ICG, 8 (6.5%) had positive node(s) identified with gamma probe signaling only, and 2 (1.6%) had positive node(s) identified with ICG only. There was an overall 21.4% SLN-positive rate, with 8% T1, 18.5% T2, 41.1% T3, and 52.4% T4, which is higher than the predicted rates for each stage. Conclusions: With the largest cohort of patients reported who underwent a melanoma SLNB with lymphoscintigraphy and ICG, we demonstrated that this technique results in higher SLN-positive rates than predicted. Patients are being followed but, given the TP data, knowledge of our results may foster the use of this modality to improve staging and treatment options.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Tumor Resection Guided by Intraoperative Indocyanine Green Dye Fluorescence Angiography Results in Negative Surgical Margins and Decreased Local Recurrence in an Orthotopic Mouse Model of Osteosarcoma

Background: Surgical resection with negative margins is the foundation of extremity sarcoma management. Failure to achieve negative surgical margins can result in local recurrence (LR), a potentially devastating complication. Indocyanine green (ICG) is a US FDA-approved fluorophore previously used to guide carcinoma resections. We investigated the potential of ICG as an intraoperative guide during experimental sarcoma resection. Methods: Fifty 6-week-old immunocompetent Balb/c female mice received left proximal tibia paraphyseal injections of 5 × 10{sup 5} K7M2 murine osteosarcoma cells. Animals were separated into two groups (n = 25 each): (1) ICG-assisted surgical resection; and (2) no ICG-assisted resection. Resections were performed 4 weeks after primary tumor engraftment. All animals received 7.5 ug ICG via retro-orbital injection 12 h prior to surgery. ICG fluorescence measurements and clinical evaluations were performed 4 weeks after resection to detect LR. Results: Eleven of 25 animals from each group developed gross tumors. Four weeks after resection, group 1 had 0/11 tumor recurrences, while group 2 had recurrences in 9/11 (81.8%) experimental mice (p < 0.0002) (Fig. 2). There was a 100% NPV in group 1, and no tumor recurrence with fluorescence-free margins after the primary surgery. Group 2 had a 100% positive predictive value for the development of an LR if any fluorescent signal was present at the surgical margin after resection. Conclusion: Intraoperative ICG guidance led to reliably negative surgical margins and a diminished LR rate. Given the benign safety profile of ICG and its prior clinical success, these results could be immediately translatable to the clinical realm.

60 APPLIED LIFE SCIENCES↗

The Sentinel Lymph Node Biopsy Using Indocyanine Green Fluorescence Plus Radioisotope Method Compared With the Radioisotope-Only Method for Breast Cancer Patients After Neoadjuvant Chemotherapy: A Prospective, Randomized, Open-Label, Single-Center Phase 2 Trial

Background: This study aimed to compare the sentinel lymph node (SLN) identification rates for breast cancer patients after neoadjuvant chemotherapy (NAC) between the dual method (DM) of indocyanine green fluorescence (ICG-F) plus a radioisotope (RI) and RI alone. Methods: This randomized study enrolled 130 patients who received NAC for breast cancer and 122 patients who received SLN biopsy (SLNB) using either DM (n = 58) or RI only (n = 64). The study compared the identification rate, number of SLNs, and detection time of SLNB. Results: Among the 122 patients, 113 (92.6%) were clinically node-positive before NAC. The SLN identification rate was 98.3% in the DM group and 93.8% in the RI group (p = 0.14). The DM group and the RI group were similar in the average number of SLNs (2.2 ± 1.13 vs. 1.9 ± 1.33; p = 0.26) and the time to detection of the first SLN (8.7 ± 4.98 vs. 8.3 ± 4.31 min; p = 0.30). In the DM group, transcutaneous lymphatic drainage was visualized by fluorescence imaging for 65.5% (38 of 58) of the patients. The SLN identification rate was 94.7% using ICG-F and 93% using RI (p = 0.79). During and after the operation, no complications, including allergic reactions or skin necrosis, occurred. Conclusions: This study is the first randomized trial to use ICG-F for SLNB in breast cancer patients after NAC. The DM including ICG-F could be a feasible and safe method for SLNB in initially node-positive breast cancer patients with NAC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green

Significance Imaging in the shortwave IR (SWIR) spectral window allows the observation of processes deep within living animals. Recent studies have shown that SWIR imaging enables unprecedented imaging opportunities, including contact-free monitoring of vital signs, generation of microvasculature blood flow maps, real-time metabolic imaging, and molecularly targeted imaging. Yet, whereas bright SWIR fluorophores have been developed for preclinical research settings, applications in the clinic have been held back by the conventional belief that no clinically approved fluorophore is available. Here, we show that indocyanine green, a clinically approved near-IR dye, exhibits a remarkable amount of SWIR emission, which enables state-of-the-art SWIR imaging with direct translation potential into clinical settings, and even outperforms other commercially available SWIR emitters.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Experimental upper bounds for resonance-enhanced entangled two-photon absorption cross section of indocyanine green

Resonant intermediate states have been proposed to increase the efficiency of entangled two-photon absorption (ETPA). Although resonance-enhanced ETPA (r-ETPA) has been demonstrated in atomic systems using bright squeezed vacuum, it has not been studied in organic molecules. We investigate for the first time r-ETPA in an organic molecular dye, indocyanine green (ICG), when excited by broadband entangled photons in near-IR. Similar to many reported virtual state mediated ETPA (v-ETPA) measurements, no r-ETPA signals are measured, with an experimental upper bound for the cross section placed at 6(±2) × 10 −23 cm 2 . In addition, the classical resonance-enhanced two-photon absorption (r-TPA) cross section of ICG at 800 nm is measured for the first time to be 20(±13) GM, where 1 GM equals 10 −50 cm 4 s, suggesting that having a resonant intermediate state does not significantly enhance two-photon processes in ICG. Furthermore, the spectrotemporally resolved emission signatures of ICG excited by entangled photons are also presented to support this conclusion.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Superconducting nanowire single-photon detector enhanced near-infrared II portable confocal microscopy for tissue imaging with indocyanine green

In this Letter a novel, to our knowledge, approach for near-infrared (NIR) fluorescence portable confocal microscopy is introduced, aiming to enhance fluorescence imaging of biological samples in the NIR-II window. By integrating a superconducting nanowire single-photon detector (SNSPD) into a confocal microscopy, we have significantly leveraged the detection efficiency of the NIR-II fluorescence signal from indocyanine green (ICG), an FDA-approved dye known for its NIR-II fluorescence capabilities. The SNSPD, characterized by its extremely low dark count rate and optimized NIR system detection efficiency, enables the excitation of ICG with 1 mW and the capture of low-light fluorescence signals from deep regions (up to 512 µm). Consequently, our technique was able to produce high-resolution images of bio samples with a superior signal-to-noise ratio, making a substantial advancement in the field of fluorescence microscopy and offering a promising opportunity for future clinical study.

Liu, Yifan (ORCID:0000000328877704)↗

Intraoperative Fluorescent Angiography Predicts Pharyngocutaneous Fistula After Salvage Laryngectomy

Background: Technology to assess tissue perfusion is exciting with translational potential, although data supporting its clinical applications have been lagging. Patients who have undergone radiation are at particular risk of poor tissue perfusion and would benefit from this expanding technology. We designed a prospective clinical trial using intraoperative indocyanine green angiography to evaluate for wound-healing complications in patients undergoing salvage laryngectomy after radiation failure. Patients and Methods: This prospective trial included patients undergoing salvage laryngectomy at a National Cancer Institute-designated tertiary cancer center between 2016 and 2018. After tumor extirpation and prior to reconstruction, 10 mg indocyanine green dye was infused and the fluorescence (F{sub HYPO}) and ingress rate of the pharyngeal mucosa recorded. The primary outcome measure was formation of a pharyngocutaneous fistula (PCF). Results: Patients who developed a PCF had significantly lower F{sub HYPO} (87 vs 172, p < 0.001) and ingress rates (6.7 vs 15.8, p = 0.043) compared with those who did not develop a fistula. There were no fistulas in patients with F{sub HYPO} > 150 (n = 21) or ingress > 15 (n = 15). There was a 50% fistula rate in patients with F{sub HYPO} ≤ 103 (n = 10) and ingress rate ≤ 6 (n = 6). Conclusions: Intraoperative indocyanine green angiography can assess hypoperfusion in patients and predict risk of PCFs after salvage laryngectomy, and can thus intraoperatively risk-stratify patients for postoperative wound-healing complications.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Robotic Extended Right Hemicolectomy with Complete Mesocolic Excision and D3 Lymph Node Dissection

Background: Recent studies have shown the benefits of complete mesocolic excision and extended lymphadenectomy (D3 lymph node dissection) in patients with colon cancer.1{sup –}3 Methods: We present the case of a 62-year-old male with hepatic flexure adenocarcinoma. No metastatic disease was identified by computed tomography. A robot-assisted extended right hemicolectomy with complete mesocolic excision, D3 lymph node dissection, and resection of the mesentery with intact visceral peritoneum was performed. Results: The trocars are placed in the right lower (8 mm), lower midline (8 mm), and left upper (12 mm) quadrants. The camera port is placed superior to the umbilicus, and the assistant port is placed in the left lower quadrant. The robotic right lower port is used to place the cecum on tension in order to outline the ileocolic pedicle. The assistant retracts the transverse colon cephalad to outline the superior mesenteric artery and vein. Using two robotic arms, the surgeon begins dissection over the superior mesenteric vein inferior to the ileocolic pedicle. Cephalad dissection along the superior mesenteric vein proceeds with reflection of the mesentery and D3 lymph nodes laterally to allow en bloc resection. The ileocolic and middle colic vessels are identified, ligated and divided at their origins. The plane is then developed between the right colon mesentery and the retroperitoneum, including Gerota’s fascia, duodenum, and head of the pancreas, in a medial-to-lateral fashion, with care taken to ensure an intact visceral peritoneum is maintained. The proximal transverse colon, hepatic flexure, and ascending colon are mobilized by taking down lateral attachments. The intervening mesentery is transected, and perfusion is assessed with indocyanine green fluorescence imaging. An intracorporeal, isoperistaltic, side-to-side anastomosis is performed using the 45-mm robotic stapler. The common enterotomy is sewn closed in two layers. Pathology showed T3N0 adenocarcinoma with all negative margins. Conclusion: Extended right hemicolectomy with complete mesocolic excision and D3 lymph node dissection is facilitated by a robotic approach, which improves visualization and instrument dexterity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Identification and Preservation of Arm Lymphatic System in Axillary Dissection for Breast Cancer to Reduce Arm Lymphedema Events: A Randomized Clinical Trial

Background: Controversy in axillary reverse mapping in axillary lymph node dissection (ALND) possibly results from incomplete recognition of the arm lymphatic system (ALS) and its compromise to oncological safety. The iDEntification and Preservation of ARm lymphaTic system (DEPART) technique facilitates complete identification of ALS; therefore, its use may decrease the occurrence of arm lymphedema. This study aimed to examine the arm lymphedema rate, locoregional recurrence, and feasibility to perform DEPART in ALND. Methods: Patients from February 2013 to October 2017 from two tertiary referral centers were randomly assigned to two groups. In the study group, indocyanine green and methylene blue (MB) were utilized to identify arm sentinel nodes, and 0.1 ml MB was injected into the arm sentinel nodes to reveal the subsequent-echelon nodes and lymphatics. Gross arm lymph nodes were examined by intraoperative partial frozen section and were removed if positive. Arm lymphedema, local recurrence, regional recurrence, and distant metastasis were recorded at different follow-up examinations. Results: Arm sentinel nodes were identified in 573 (83.2%) patients. Subsequent-echelon nodes and lymphatics were visualized in 558 (97.4%) patients. Metastatic arm nodes were identified in 38 (6.8%) patients. The arm lymphedema rate was 3.3% (18/543) in the study group versus 15.3% (99/648) in the control group (p < 0.001) after 37-month median follow-up. Regional recurrence showed no difference between the two groups (1.4% and 1.2%, respectively) (p = 0.392). Conclusions: DEPART can benefit breast cancer patients who undergo ALND, reducing the arm lymphedema rate without adversely affecting the morbidity of regional recurrence.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Narrow-Band Imaging Improves Detection of Colorectal Peritoneal Metastases: A Clinical Study Comparing Advanced Imaging Techniques

Background: Colorectal peritoneal metastases (PM) are often diagnosed in an advanced disease stage. Cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) improve survival of patients with colorectal PM, although most benefit is seen in patients with limited peritoneal disease. Advanced imaging techniques might improve the detection of PM, potentially leading to earlier diagnosis and improved cytoreduction. This prospective clinical trial compared three advanced techniques with conventional white-light imaging for the detection of colorectal PM: narrow-band imaging (NBI), near-infrared indocyanine green fluorescent imaging (NIR-ICG), and spray-dye chromoendoscopy (SDCE). Methods: Patients with colorectal PM were prospectively included. Prior to cytoreduction and HIPEC, all abdominal regions were inspected with white-light imaging, NBI, NIR-ICG, and SDCE during exploratory laparoscopy. Primary endpoints were sensitivity and specificity for the detection of PM, using pathological examination of biopsied lesions as the reference standard. The safety of all techniques was assessed. Results: Between May 2016 and March 2018, four different techniques were analyzed in 28 patients, resulting in 169 biopsies. Sensitivity for the detection of PM significantly increased from 80.0% with white light to 96.0% with NBI (p = 0.008), without loss of specificity (74.8% vs. 73.1%, respectively, p = 0.804). The use of NIR-ICG and SDCE was discontinued after 10 patients had undergone treatment because the lesions were not fluorescent using NIR-ICG, and because SDCE did not visualize the whole peritoneum. No adverse events relating to the imaging techniques occurred. Conclusion: NBI substantially increased the detection of PM. This method is safe and could improve the detection of metastatic lesions and help optimize cytoreduction in patients with colorectal PM.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Laparoscopic Isolated Total Caudate Lobectomy for Hepatocellular Carcinoma Located in the Paracaval Portion of the Cirrhotic Liver

Background: Despite the widespread use of laparoscopic hepatectomies in past decades, laparoscopic isolated total caudate lobectomy for hepatocellular carcinoma (HCC) remains challenging,{sup 1,2} especially for patients with cirrhosis. Moreover, a laparoscopic isolated total caudate lobectomy for HCC originating in the paracaval portion of the caudate lobe is very rare. We herein present a video showing laparoscopic total caudate lobectomy for a cirrhotic patient with HCC located in the paracaval portion of the caudate lobe. Methods: A 58-year-old woman who suffered from hepatitis C virus-related cirrhosis was admitted to our institution. The preoperative computed tomography showed a 2.5 × 2.0 cm liver mass located in segment I that was very close to the right hepatic pedicle. Although her liver function was Child–Pugh A, the indocyanine green (ICG)-15 test was high at 10.9%. Right hepatectomy plus caudate lobectomy was not adopted because of the severe cirrhosis and the elevated ICG-15. Thus, laparoscopic isolated total caudate lobectomy was contemplated. Results: The patient was placed in the supine position. After full mobilization, the caudate lobe was exposed. The third porta of the liver was then dissected and the short hepatic veins were controlled with clips and LigaSure. The dissection was finished when the whole third porta of the liver was freed. Subsequently, the portal branches to the caudate lobe were ligated and cut. The combination between the left- and right-sided laparoscopic approaches was used to transect liver parenchyma. The superficial parenchyma was divided using an harmonic scalpel, while the deeper tissue was divided using a Cavitron ultrasonic aspirator (CUSA). The Pringle maneuver was used intermittently during the parenchymal transection as necessary. In the left-sided approach, the caudate lobe was resected along the left and middle hepatic vein toward the right side, to expose the dorsal semicircle of the right hepatic vein. In the right-sided approach, the resection started from the right border of the process portion to the root of the right hepatic vein in the cranial direction. Finally, the whole caudate lobe was resected and the three main hepatic veins were exposed on the cutting plane. The specimen was removed from suprapubic incision. The operative time was 300 min and the total Pringle time was 50 min. The postoperative course was uneventful. Conclusions: A laparoscopic isolated total caudate lobectomy for HCC located in the paracaval portion of the cirrhotic liver seems to be feasible and safe in selected patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Multihead Attention U‐Net for Magnetic Particle Imaging–Computed Tomography Image Segmentation

Magnetic particle imaging (MPI) is an emerging noninvasive molecular imaging modality with high sensitivity and specificity, exceptional linear quantitative ability, and potential for successful applications in clinical settings. Computed tomography (CT) is typically combined with the MPI image to obtain more anatomical information. Herein, a deep learning‐based approach for MPI‐CT image segmentation is presented. The dataset utilized in training the proposed deep learning model is obtained from a transgenic mouse model of breast cancer following administration of indocyanine green (ICG)‐conjugated superparamagnetic iron oxide nanoworms (NWs‐ICG) as the tracer. The NWs‐ICG particles progressively accumulate in tumors due to the enhanced permeability and retention (EPR) effect. The proposed deep learning model exploits the advantages of the multihead attention mechanism and the U‐Net model to perform segmentation on the MPI‐CT images, showing superb results. In addition, the model is characterized with a different number of attention heads to explore the optimal number for our custom MPI‐CT dataset.

Juhong, Aniwat↗

The Potential for Midtreatment Albumin-Bilirubin (ALBI) Score to Individualize Liver Stereotactic Body Radiation Therapy

Our individualized functional response adaptive approach to liver stereotactic body radiation therapy (SBRT) with assessment of indocyanine green (ICG) retention at baseline and midtreatment to detect subclinical changes in liver function, permitting dose adjustment, has decreased toxicity while preserving efficacy. We hypothesized that assessment of the albumin-bilirubin (ALBI) score at baseline and midtreatment would allow for more practical identification of patients at risk for treatment-related toxicity (TRT).

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dynamic and accurate assessment of acetaminophen-induced hepatotoxicity by integrated photoacoustic imaging and mechanistic biomarkers in vivo

The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational non-invasive photoacoustic imaging of liver function with mechanistic circulating biomarkers of hepatotoxicity with histological assessment to facilitate the more accurate and precise characterization of APAP-ILI and the efficacy of therapeutic intervention. Perturbation of liver function and cellular viability was assessed in C57BL/6J male mice by Indocyanine green (ICG) clearance (Multispectral Optoacoustic Tomography (MSOT)) and by measurement of mechanistic (miR-122, HMGB1) and established (ALT, bilirubin) circulating biomarkers in response to the acetaminophen and its treatment with acetylcysteine (NAC) in vivo. We utilised a 60% partial hepatectomy model as a situation of defined hepatic functional mass loss to compared acetaminophen-induced changes to. Integration of these mechanistic markers correlated with histological features of APAP hepatotoxicity in a time-dependent manner. They accurately reflected the onset and recovery from hepatotoxicity compared to traditional biomarkers and also reported the efficacy of NAC with high sensitivity. ICG clearance kinetics correlated with histological scores for acute liver damage for APAP (i.e. 3 h timepoint; r = 0.90, P < 0.0001) and elevations in both of the mechanistic biomarkers, miR-122 (e.g. 6 h timepoint; r = 0.70, P = 0.005) and HMGB1 (e.g. 6 h timepoint; r = 0.56, P = 0.04). For the first time we report the utility of this non-invasive longitudinal imaging approach to provide direct visualisation of the liver function coupled with mechanistic biomarkers, in the same animal, allowing the investigation of the toxicological and pharmacological aspects of APAP-ILI and hepatic regeneration. - Highlights: • Imaging and circulating biomarker “tool box” proposed for liver injury and repair. • Liver function monitored in real time during acetaminophen hepatotoxicity. • Approach based on ICG clearance measured by MSOT. • ICG kinetics correlates with established methods for liver injury detection. • Approach can be used for prediction of response to therapeutic interventions.

60 APPLIED LIFE SCIENCES↗