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Toward optimization of imaging system and lymphatic tracer for near-infrared fluorescent sentinel lymph node mapping in breast cancer.

Mieog JS, Troyan SL, Hutteman M, Donohoe KJ, van der Vorst JR, Stockdale A, Liefers GJ, Choi HS, Gibbs-Strauss SL, Putter H, Gioux S, Kuppen PJ, Ashitate Y, Löwik CW, Smit VT, Oketokoun R, Ngo LH, van de Velde CJ, Frangioni JV, Vahrmeijer AL - Ann. Surg. Oncol. (2011)

Bottom Line: Contrast agent quenching at the injection site and dilution within lymphatic channels were major contributors to signal strength of the SLN.Optimal injection dose of ICG:HSA ranged between 400 and 800 μM.No adverse reactions were observed.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.

ABSTRACT

Background: Near-infrared (NIR) fluorescent sentinel lymph node (SLN) mapping in breast cancer requires optimized imaging systems and lymphatic tracers.

Materials and methods: A small, portable version of the FLARE imaging system, termed Mini-FLARE, was developed for capturing color video and two semi-independent channels of NIR fluorescence (700 and 800 nm) in real time. Initial optimization of lymphatic tracer dose was performed using 35-kg Yorkshire pigs and a 6-patient pilot clinical trial. More refined optimization was performed in 24 consecutive breast cancer patients. All patients received the standard of care using (99m)Technetium-nanocolloid and patent blue. In addition, 1.6 ml of indocyanine green adsorbed to human serum albumin (ICG:HSA) was injected directly after patent blue at the same location. Patients were allocated to 1 of 8 escalating ICG:HSA concentration groups from 50 to 1000 μM.

Results: The Mini-FLARE system was positioned easily in the operating room and could be used up to 13 in. from the patient. Mini-FLARE enabled visualization of lymphatic channels and SLNs in all patients. A total of 35 SLNs (mean = 1.45, range 1-3) were detected: 35 radioactive (100%), 30 blue (86%), and 35 NIR fluorescent (100%). Contrast agent quenching at the injection site and dilution within lymphatic channels were major contributors to signal strength of the SLN. Optimal injection dose of ICG:HSA ranged between 400 and 800 μM. No adverse reactions were observed.

Conclusions: We describe the clinical translation of a new NIR fluorescence imaging system and define the optimal ICG:HSA dose range for SLN mapping in breast cancer.

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Related in: MedlinePlus

Real-time NIR fluorescence imaging during sentinel lymph node mapping in women with breast cancer: Shown are typical in vivo (top row) and ex vivo (bottom row; postresection) results from a subject injected with 500 μM ICG:HSA. White arrow identifies the SLN. NIR fluorescence (left) and pseudocolored (lime green) merge with the color video image (right). Exposure times were 50 ms for in vivo images and 30 ms for ex vivo images. 760 nm excitation fluence rate was ~7.7 mW/cm2 for all images. Scale bars indicate 1 cm
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Fig3: Real-time NIR fluorescence imaging during sentinel lymph node mapping in women with breast cancer: Shown are typical in vivo (top row) and ex vivo (bottom row; postresection) results from a subject injected with 500 μM ICG:HSA. White arrow identifies the SLN. NIR fluorescence (left) and pseudocolored (lime green) merge with the color video image (right). Exposure times were 50 ms for in vivo images and 30 ms for ex vivo images. 760 nm excitation fluence rate was ~7.7 mW/cm2 for all images. Scale bars indicate 1 cm

Mentions: This study aimed to test the feasibility of NIR fluorescence in SLN detection, using ICG:HSA and the Mini-FLARE, in direct comparison with the conventional lymphatic tracers radiocolloid and patent blue. A total of 24 consecutive breast cancer patients underwent standard-of-care SLN mapping with the addition of preoperative ICG:HSA injection and subsequent intraoperative NIR fluorescence imaging. Patient and tumor characteristics are provided in Table 2. Use of the Mini-FLARE during surgery did not interfere with the standard of care. Average time between ICG:HSA injection and skin incision was 16 ± 3 min (Table 3). In all patients (N = 24), NIR fluorescence imaging enabled visualization of the SLN (Fig. 3). A total of 35 SLNs were identified, which were all radioactive and NIR fluorescent (Table 3). There were 5 SLNs from 4 patients that did not have blue staining from patent blue. In all patients, the NIR fluorescence signal in the SLN was detected before patent blue. Average time between skin incision and resection of the first SLN was 17 ± 5 min. After all nodes detected using NIR fluorescence were resected, the axilla was systematically inspected for any remaining radioactivity. No additional radioactive nodes were identified that were not detected by NIR fluorescence. No adverse reactions associated with the use of ICG:HSA or the Mini-FLARE occurred. Two patients experienced a wound infection requiring antibiotics, and one patient underwent surgical re-exploration because of an expanding hematoma following axillary lymph node dissection (Table 3).Table 2


Toward optimization of imaging system and lymphatic tracer for near-infrared fluorescent sentinel lymph node mapping in breast cancer.

Mieog JS, Troyan SL, Hutteman M, Donohoe KJ, van der Vorst JR, Stockdale A, Liefers GJ, Choi HS, Gibbs-Strauss SL, Putter H, Gioux S, Kuppen PJ, Ashitate Y, Löwik CW, Smit VT, Oketokoun R, Ngo LH, van de Velde CJ, Frangioni JV, Vahrmeijer AL - Ann. Surg. Oncol. (2011)

Real-time NIR fluorescence imaging during sentinel lymph node mapping in women with breast cancer: Shown are typical in vivo (top row) and ex vivo (bottom row; postresection) results from a subject injected with 500 μM ICG:HSA. White arrow identifies the SLN. NIR fluorescence (left) and pseudocolored (lime green) merge with the color video image (right). Exposure times were 50 ms for in vivo images and 30 ms for ex vivo images. 760 nm excitation fluence rate was ~7.7 mW/cm2 for all images. Scale bars indicate 1 cm
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3139732&req=5

Fig3: Real-time NIR fluorescence imaging during sentinel lymph node mapping in women with breast cancer: Shown are typical in vivo (top row) and ex vivo (bottom row; postresection) results from a subject injected with 500 μM ICG:HSA. White arrow identifies the SLN. NIR fluorescence (left) and pseudocolored (lime green) merge with the color video image (right). Exposure times were 50 ms for in vivo images and 30 ms for ex vivo images. 760 nm excitation fluence rate was ~7.7 mW/cm2 for all images. Scale bars indicate 1 cm
Mentions: This study aimed to test the feasibility of NIR fluorescence in SLN detection, using ICG:HSA and the Mini-FLARE, in direct comparison with the conventional lymphatic tracers radiocolloid and patent blue. A total of 24 consecutive breast cancer patients underwent standard-of-care SLN mapping with the addition of preoperative ICG:HSA injection and subsequent intraoperative NIR fluorescence imaging. Patient and tumor characteristics are provided in Table 2. Use of the Mini-FLARE during surgery did not interfere with the standard of care. Average time between ICG:HSA injection and skin incision was 16 ± 3 min (Table 3). In all patients (N = 24), NIR fluorescence imaging enabled visualization of the SLN (Fig. 3). A total of 35 SLNs were identified, which were all radioactive and NIR fluorescent (Table 3). There were 5 SLNs from 4 patients that did not have blue staining from patent blue. In all patients, the NIR fluorescence signal in the SLN was detected before patent blue. Average time between skin incision and resection of the first SLN was 17 ± 5 min. After all nodes detected using NIR fluorescence were resected, the axilla was systematically inspected for any remaining radioactivity. No additional radioactive nodes were identified that were not detected by NIR fluorescence. No adverse reactions associated with the use of ICG:HSA or the Mini-FLARE occurred. Two patients experienced a wound infection requiring antibiotics, and one patient underwent surgical re-exploration because of an expanding hematoma following axillary lymph node dissection (Table 3).Table 2

Bottom Line: Contrast agent quenching at the injection site and dilution within lymphatic channels were major contributors to signal strength of the SLN.Optimal injection dose of ICG:HSA ranged between 400 and 800 μM.No adverse reactions were observed.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.

ABSTRACT

Background: Near-infrared (NIR) fluorescent sentinel lymph node (SLN) mapping in breast cancer requires optimized imaging systems and lymphatic tracers.

Materials and methods: A small, portable version of the FLARE imaging system, termed Mini-FLARE, was developed for capturing color video and two semi-independent channels of NIR fluorescence (700 and 800 nm) in real time. Initial optimization of lymphatic tracer dose was performed using 35-kg Yorkshire pigs and a 6-patient pilot clinical trial. More refined optimization was performed in 24 consecutive breast cancer patients. All patients received the standard of care using (99m)Technetium-nanocolloid and patent blue. In addition, 1.6 ml of indocyanine green adsorbed to human serum albumin (ICG:HSA) was injected directly after patent blue at the same location. Patients were allocated to 1 of 8 escalating ICG:HSA concentration groups from 50 to 1000 μM.

Results: The Mini-FLARE system was positioned easily in the operating room and could be used up to 13 in. from the patient. Mini-FLARE enabled visualization of lymphatic channels and SLNs in all patients. A total of 35 SLNs (mean = 1.45, range 1-3) were detected: 35 radioactive (100%), 30 blue (86%), and 35 NIR fluorescent (100%). Contrast agent quenching at the injection site and dilution within lymphatic channels were major contributors to signal strength of the SLN. Optimal injection dose of ICG:HSA ranged between 400 and 800 μM. No adverse reactions were observed.

Conclusions: We describe the clinical translation of a new NIR fluorescence imaging system and define the optimal ICG:HSA dose range for SLN mapping in breast cancer.

Show MeSH
Related in: MedlinePlus