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An urgent clinical need exists for real-time intraoperative visualization of breast carcinomas during BCS. We previously demonstrated the ability of a prototype imaging device to identify breast carcinoma in excised surgical specimens following 5-aminolevulinic acid (5-ALA) administration. However, this prototype device was not designed to image the surgical cavity for remaining carcinoma after the excised lumpectomy\u00a0specimen is removed. A new handheld fluorescence (FL) imaging prototype device, designed to image both excised specimens and within the surgical cavity, was assessed in a clinical trial to evaluate its clinical utility for first-in-human, real-time intraoperative imaging during index BCS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The imaging device combines consumer-grade imaging sensory technology with miniature light-emitting diodes (LEDs) and multiband optical filtering to capture high-resolution white light (WL) and FL digital images and videos. The technology allows for visualization of protoporphyrin IX (PpIX), which fluoresces red when excited by violet-blue light. To date,\n                      <jats:inline-formula>\n                        <jats:alternatives>\n                          <jats:tex-math>$$n = 17$$<\/jats:tex-math>\n                          <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                            <mml:mrow>\n                              <mml:mi>n<\/mml:mi>\n                              <mml:mo>=<\/mml:mo>\n                              <mml:mn>17<\/mml:mn>\n                            <\/mml:mrow>\n                          <\/mml:math>\n                        <\/jats:alternatives>\n                      <\/jats:inline-formula>\n                      patients have received\n                      <jats:inline-formula>\n                        <jats:alternatives>\n                          <jats:tex-math>$$20\\frac{\\text {mg}}{\\textrm{kg}}$$<\/jats:tex-math>\n                          <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                            <mml:mrow>\n                              <mml:mn>20<\/mml:mn>\n                              <mml:mfrac>\n                                <mml:mtext>mg<\/mml:mtext>\n                                <mml:mtext>kg<\/mml:mtext>\n                              <\/mml:mfrac>\n                            <\/mml:mrow>\n                          <\/mml:math>\n                        <\/jats:alternatives>\n                      <\/jats:inline-formula>\n                      bodyweight (BW) 5-ALA orally 2-4 h before imaging to facilitate the accumulation of PpIX within tumour cells. Tissue types were identified based on their colour appearance. Breast tumours in sectioned lumpectomies appeared red, which contrasted against the green connective tissues and orange-brown adipose tissues. In addition, ductal carcinoma\n                      <jats:italic>in situ<\/jats:italic>\n                      (DCIS) that was missed during intraoperative standard of care was identified at the surgical margin at &lt;1 mm depth. In addition, artifacts due to the surgical drape, illumination, and blood within the surgical cavity were discovered.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study has demonstrated the detection of a grossly occult positive margin intraoperatively. Artifacts from imaging within the surgical cavity have been identified, and potential mitigations have been proposed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>Identifier:  (Trial start date is September 2010. It was registered to ClinicalTrials.gov retrospectively on April 23, 2013, then later updated on April 9, 2020, to reflect the introduction of the new imaging device.)<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s42490-024-00079-9","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T21:04:14Z","timestamp":1717189454000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A handheld device for intra-cavity and ex vivo fluorescence imaging of breast conserving surgery margins with 5-aminolevulinic acid"],"prefix":"10.1186","volume":"6","author":[{"given":"Christopher","family":"Gibson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley C.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arcturus","family":"Phoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayana","family":"Thalanki\u00a0Anantha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Ottolino-Perry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Petropoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuha","family":"Qureshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasanth","family":"Subramanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anam","family":"Shahid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Carcone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Tsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayleen","family":"Sukhram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fannong","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan\u00a0J.","family":"Done","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra\u00a0M.","family":"Easson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tulin","family":"Cil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Reedijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wey\u00a0L.","family":"Leong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph\u00a0S.","family":"DaCosta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,1]]},"reference":[{"issue":"2","key":"79_CR1","doi-asserted-by":"publisher","first-page":"E102","DOI":"10.9778\/cmajo.20130025","volume":"2","author":"G Porter","year":"2014","unstructured":"Porter G, Wagar B, Bryant H, Hewitt M, Wai E, Dabbs K, et al. 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Informed consent was obtained from all subjects involved in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"RSD, KOP, CG, NTA, WLL, AME, and SJD are co-inventors on IP licensed to MolecuLight Inc. (Toronto, Canada) and photonamic GmbH & Co. KG (Pinneberg, Germany) commercializing this technology. These individuals were not involved with participant recruitment. This study was a UHN investigator-sponsored trial (clinicaltrials.gov identifier NCT01837225) prior to IP licensing. RSD is the Founder, Chief Scientific Officer, Board member, and Shareholder of MolecuLight Inc. MolecuLight staff were not involved directly or indirectly with this study. RSD participated in the conception and design of the study, and reviewed and edited the final manuscript. He did not recruit nor consent patients, nor collect, nor analyze data resulting from the study. 5-ALA HCl was provided by photonamic GmbH and Co. KG (Pinneberg, Germany) governed by a Drug Transfer Agreement between UHN and photonamic. RSD is the Chief Executive Officer of and holds interest in photonamic GmbH & Co. KG\u2019s subsidiary company (SBI ALApharma Canada Inc., Toronto, Canada) developing this technology for commercialization. RSD\u2019s potential conflicts of interest are governed by a UHN Conflict of Interest Management Plan. At the time of publishing, KOP is employed by and holds an interest in SBI ALApharma Canada Inc., however, was wholly employed by UHN with no COI at the time of her contributions to this study. All other authors declare that they have no competing interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5"}}