Intraoperative Near-Infrared Imaging Can Identify Pulmonary Nodules

doi:10.1016/j.athoracsur.2014.05.026

The Annals of Thoracic Surgery

Volume 98, Issue 4, October 2014, Pages 1223-1230

https://doi.org/10.1016/j.athoracsur.2014.05.026 Get rights and content

Background

Over 80,000 people undergo pulmonary resection for a lung nodule in the United States each year. Small nodules are frequently missed or difficult to find despite preoperative imaging. We hypothesized that near-infrared (NIR) imaging technology could be used to identify and locate lung nodules during surgery.

Methods

We enrolled 18 patients who were diagnosed with a pulmonary nodule that required resection. All patients had a fine-cut 1-mm computed tomography scan preoperatively. The patients were given systemic 5 mg/kg indocyanine green and then underwent an open thoracotomy 24 hours later. The NIR imaging was used to identify the primary nodule and search for additional nodules that were not found by visual inspection or manual palpation of the ipsilateral lung.

Results

Manual palpation and visual inspection identified all 18 primary pulmonary nodules and no additional lesions. Intraoperative NIR imaging detected 16 out of the 18 primary nodules. The NIR imaging also identified 5 additional subcentimeter nodules; 3 metastatic adenocarcinomas and 2 metastatic sarcomas. This technology could identify nodules as small as 0.2 cm and as deep as 1.3 cm from the pleural surface. This approach discovered 3 nodules that were in different lobes than the primary tumor. Nodule fluorescence was independent of size, metabolic activity, histology, tumor grade and vascularity.

Conclusions

This is the first-in-human demonstration of identifying pulmonary nodules during thoracic surgery with NIR imaging without a priori knowledge of their location or existence. The NIR imaging can detect pulmonary nodules during lung resections that are poorly visualized on computed tomography and difficult to discriminate on finger palpation.

Section snippets

Study Design

This study was approved by the University of Pennsylvania Institutional Review Board and all patients gave informed consent. Any patient with a solitary lung nodule and who was enrolled for surgery was eligible for this study. All patients underwent computed tomography (CT) scanning with at least 0.1 cm slice thickness. The CT scan was reviewed by a radiologist to confirm the presence of a solitary pulmonary nodule. The patients were specifically consented for the possibility that additional

Near-Infrared Imaging Can Identify Pulmonary Nodules Intraoperatively

Between January and July 2012, 18 patients between the ages of 29 and 78 (mean 60) with a diagnosis of a solitary pulmonary nodule were evaluated in a thoracic surgical clinic (Table 1). A 1-mm fine-cut CT scan demonstrated a single pulmonary nodule or mass (0.8 to 11 cm, mean 2.8 cm). Due to surgeon and patient preference, 8 out of 18 patients had a preoperative biopsy by transthoracic or transbronchial needle aspiration that confirmed a neoplasm. The remaining 10 patients did not have a

Comment

The goal of this study was to determine if NIR imaging could identify pulmonary nodules during a lung resection. In this pilot study, 18 patients with a solitary pulmonary nodule underwent a thoracotomy after systemic injection of 5 mg/kg ICG. The NIR signal detected 91% of these primary nodules suggesting colocalization of the ICG to the nodules, and fluorescent microscopy confirmed the ICG was in the tumors. The NIR imaging interestingly also detected 5 additional nodules. The sensitivity for

References (25)

R.J. Cerfolio et al.
Is palpation of the nonresected pulmonary lobe(s) required for patients with non-small cell lung cancer? A prospective study
J Thorac Cardiovasc Surg
(2008)
R.J. Cerfolio et al.
A prospective study to determine the incidence of non-imaged malignant pulmonary nodules in patients who undergo metastasectomy by thoracotomy with lung palpation
Ann Thorac Surg
(2011)
M.C. Ellis et al.
Comparison of pulmonary nodule detection rates between preoperative ct imaging and intraoperative lung palpation
Am J Surg
(2011)
P.M. McCormack et al.
Role of video-assisted thoracic surgery in the treatment of pulmonary metastases: results of a prospective trial
Ann Thorac Surg
(1996)
2013 United States Procedure Volumes Database. Thomson Reuters. United States; 2013. Available at:...
National Inpatient Sample (NIS). Agency for healthcare research and quality. 2011. Available at...
R.J. Cerfolio et al.
Non-imaged pulmonary nodules discovered during thoracotomy for metastasectomy by lung palpation
Eur J Cardiothorac Surg
(2009)
S. Diederich et al.
Solitary pulmonary nodule: detection and management
Cancer Imaging
(2006)
T.C. Mineo et al.
Transxiphoid bilateral palpation in video-assisted thoracoscopic lung metastasectomy
Arch Surg
(2001)
G.M. van Dam et al.
Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-alpha targeting: first in-human results
Nat Med
(2011)

J.R. van der Vorst et al.

Near-infrared fluorescence-guided resection of colorectal liver metastases

Cancer

(2013)

B. Madajewski et al.

Intraoperative near-infrared imaging of surgical wounds after tumor resections can detect residual disease

Clin Cancer Res

(2012)

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The diagnostic yield of bronchoscopy is not satisfactory, even with recent navigation technologies, especially for tumors located outside of the bronchial lumen. Our objective was to perform a preclinical assessment of folate receptor–targeted near-infrared imaging-guided bronchoscopy to detect peribronchial tumors.
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Original articleGeneral thoracicIntraoperative Near-Infrared Imaging Can Identify Pulmonary Nodules

Background

Methods

Results

Conclusions

Section snippets

Study Design

Near-Infrared Imaging Can Identify Pulmonary Nodules Intraoperatively

Comment

J Thorac Cardiovasc Surg

Ann Thorac Surg

Am J Surg

Ann Thorac Surg

Non-imaged pulmonary nodules discovered during thoracotomy for metastasectomy by lung palpation

Eur J Cardiothorac Surg

Solitary pulmonary nodule: detection and management

Cancer Imaging

Transxiphoid bilateral palpation in video-assisted thoracoscopic lung metastasectomy

Arch Surg

Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-alpha targeting: first in-human results

Nat Med

Near-infrared fluorescence-guided resection of colorectal liver metastases

Cancer

Intraoperative near-infrared imaging of surgical wounds after tumor resections can detect residual disease

Clin Cancer Res

Original article
General thoracic
Intraoperative Near-Infrared Imaging Can Identify Pulmonary Nodules