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Cerenkov luminescence imaging (CLI) for image-guided cancer surgery

View Article: PubMed Central - PubMed

ABSTRACT

Cerenkov luminescence imaging (CLI) is a novel molecular optical imaging technique based on the detection of optical Cerenkov photons emitted by positron emission tomography (PET) imaging agents. The ability to use clinically approved tumour-targeted tracers in combination with small-sized imaging equipment makes CLI a particularly interesting technique for image-guided cancer surgery. The past few years have witnessed a rapid increase in proof-of-concept preclinical studies in this field, and several clinical trials are currently underway. This article provides an overview of the basic principles of Cerenkov radiation and outlines the challenges of CLI-guided surgery for clinical use. The preclinical and clinical trial literature is examined including applications focussed on image-guided lymph node detection and Cerenkov luminescence endoscopy, and the ongoing clinical studies and technological developments are highlighted. By intraoperatively guiding the oncosurgeon towards more accurate and complete resections, CLI has the potential to transform current surgical practice, and improve oncological and cosmetic outcomes for patients.

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Wide local excision specimen from a patient with a 22 mm, grade 2, ER+/HER2− invasive lobular carcinoma. The specimen was incised to expose the primary tumour and margins of excision, and subsequently scanned with the investigational CLI camera. a Cerenkov image, b white-light photograph (black and white) overlaid with Cerenkov signal. An increased radiance from the tumour is visible (white arrows); mean radiance is 544.0 (SD 71.0) photons/s/cm2/sr. The tumour-to-tissue background ratio is 2.44. Phosphorescent signals from the pathology inks used to orientate the specimen prior to incision are also present (open arrows). The posterior margin (blue) and superior margin (green) are visible; both margins were clear (≥5 mm) on CLI and histopathology, respectively
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Fig4: Wide local excision specimen from a patient with a 22 mm, grade 2, ER+/HER2− invasive lobular carcinoma. The specimen was incised to expose the primary tumour and margins of excision, and subsequently scanned with the investigational CLI camera. a Cerenkov image, b white-light photograph (black and white) overlaid with Cerenkov signal. An increased radiance from the tumour is visible (white arrows); mean radiance is 544.0 (SD 71.0) photons/s/cm2/sr. The tumour-to-tissue background ratio is 2.44. Phosphorescent signals from the pathology inks used to orientate the specimen prior to incision are also present (open arrows). The posterior margin (blue) and superior margin (green) are visible; both margins were clear (≥5 mm) on CLI and histopathology, respectively

Mentions: The successful applications of CLI for image-guided cancer surgery have resulted in several clinical studies that are currently ongoing to evaluate the feasibility of this technique in different tumour types. At Guy’s Hospital (London, UK), a first-in-woman pilot study evaluates intraoperative CLI for measuring tumour resection margins and lymph node status in 30 patients undergoing breast-conserving surgery (BCS) (ClinicalTrials.gov identifier NCT02037269). Patients receive an intravenous standard of care PET dose of 5 MBq/kg 18F-FDG, and excised wide local excision (WLE) specimens and lymph nodes are imaged within 1–3 h post-injection using an investigational intraoperative CLI specimen camera (Lightpoint Medical Ltd, UK) (Fig. 3). The investigational CLI camera consists of a light-tight sample chamber, a radiation-shielded thermoelectrically-cooled EMCCD camera, and a f/0.95 lens. The camera provides 8 × 8 cm field of view and 156 µm intrinsic spatial resolution. Interim results show that elevated radiances are detected in cancer compared to normal breast tissue, and that the radiation exposure to surgical staff is low [55, 56]. The results from comparing CLI resection margin status and lymph node status to the gold-standard, histopathology, are being prepared for publication at the time of writing. An example of a CLI image from a WLE specimen that was scanned intraoperatively in this clinical study is shown in Fig. 4. This image illustrates that CLI provides high-resolution functional information that allows surgeons to accurately assess tumour margins during surgery.Fig. 3


Cerenkov luminescence imaging (CLI) for image-guided cancer surgery
Wide local excision specimen from a patient with a 22 mm, grade 2, ER+/HER2− invasive lobular carcinoma. The specimen was incised to expose the primary tumour and margins of excision, and subsequently scanned with the investigational CLI camera. a Cerenkov image, b white-light photograph (black and white) overlaid with Cerenkov signal. An increased radiance from the tumour is visible (white arrows); mean radiance is 544.0 (SD 71.0) photons/s/cm2/sr. The tumour-to-tissue background ratio is 2.44. Phosphorescent signals from the pathology inks used to orientate the specimen prior to incision are also present (open arrows). The posterior margin (blue) and superior margin (green) are visible; both margins were clear (≥5 mm) on CLI and histopathology, respectively
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Related In: Results  -  Collection

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Fig4: Wide local excision specimen from a patient with a 22 mm, grade 2, ER+/HER2− invasive lobular carcinoma. The specimen was incised to expose the primary tumour and margins of excision, and subsequently scanned with the investigational CLI camera. a Cerenkov image, b white-light photograph (black and white) overlaid with Cerenkov signal. An increased radiance from the tumour is visible (white arrows); mean radiance is 544.0 (SD 71.0) photons/s/cm2/sr. The tumour-to-tissue background ratio is 2.44. Phosphorescent signals from the pathology inks used to orientate the specimen prior to incision are also present (open arrows). The posterior margin (blue) and superior margin (green) are visible; both margins were clear (≥5 mm) on CLI and histopathology, respectively
Mentions: The successful applications of CLI for image-guided cancer surgery have resulted in several clinical studies that are currently ongoing to evaluate the feasibility of this technique in different tumour types. At Guy’s Hospital (London, UK), a first-in-woman pilot study evaluates intraoperative CLI for measuring tumour resection margins and lymph node status in 30 patients undergoing breast-conserving surgery (BCS) (ClinicalTrials.gov identifier NCT02037269). Patients receive an intravenous standard of care PET dose of 5 MBq/kg 18F-FDG, and excised wide local excision (WLE) specimens and lymph nodes are imaged within 1–3 h post-injection using an investigational intraoperative CLI specimen camera (Lightpoint Medical Ltd, UK) (Fig. 3). The investigational CLI camera consists of a light-tight sample chamber, a radiation-shielded thermoelectrically-cooled EMCCD camera, and a f/0.95 lens. The camera provides 8 × 8 cm field of view and 156 µm intrinsic spatial resolution. Interim results show that elevated radiances are detected in cancer compared to normal breast tissue, and that the radiation exposure to surgical staff is low [55, 56]. The results from comparing CLI resection margin status and lymph node status to the gold-standard, histopathology, are being prepared for publication at the time of writing. An example of a CLI image from a WLE specimen that was scanned intraoperatively in this clinical study is shown in Fig. 4. This image illustrates that CLI provides high-resolution functional information that allows surgeons to accurately assess tumour margins during surgery.Fig. 3

View Article: PubMed Central - PubMed

ABSTRACT

Cerenkov luminescence imaging (CLI) is a novel molecular optical imaging technique based on the detection of optical Cerenkov photons emitted by positron emission tomography (PET) imaging agents. The ability to use clinically approved tumour-targeted tracers in combination with small-sized imaging equipment makes CLI a particularly interesting technique for image-guided cancer surgery. The past few years have witnessed a rapid increase in proof-of-concept preclinical studies in this field, and several clinical trials are currently underway. This article provides an overview of the basic principles of Cerenkov radiation and outlines the challenges of CLI-guided surgery for clinical use. The preclinical and clinical trial literature is examined including applications focussed on image-guided lymph node detection and Cerenkov luminescence endoscopy, and the ongoing clinical studies and technological developments are highlighted. By intraoperatively guiding the oncosurgeon towards more accurate and complete resections, CLI has the potential to transform current surgical practice, and improve oncological and cosmetic outcomes for patients.

No MeSH data available.


Related in: MedlinePlus