Cancer is the leading health problem in the world. Only in the EU-27 each year are 2.7 million people diagnosed with cancer, while 1.3 million die from the disease.1 To deal with cancer, knowledge of cancer physiology is essential, where tissue perfusion is one of the most important physiological parameters. Perfusion of tumors is critical in their development and growth. Early studies have shown that tumor growth is dependent on the development of vasculature that has the capacity to supply oxygen and nutrients to dividing tumor cells.2 However, the vasculature is important not only for the supply of oxygen to tumors but also for the delivery of drugs into tumors.3 Finally, vasculature is also important for the response of tumors to surgery and other ablative techniques, such as radiotherapy and thermal and nonthermal ablative techniques.4, 5
It was demonstrated that information about the tumor and healthy tissue perfusion can improve therapy outcome either by guiding tumor resection6, 7 or monitoring the reperfusion of the resected tissues (e.g., anastomosis or tissue flaps).4, 5 Conventional techniques for perfusion imaging in oncology are CT and MR imaging.10 CT perfusion imaging provides information on tissue hemodynamics by analyzing the first passage of an intravenous contrast bolus through the vessels. On the other hand, MR perfusion imaging utilizes either endogenous or exogenous tracers. In the latter case, it is based on following an injected bolus of contrast agent over time, which is then used to determine the perfusion characteristics of tissues. While both imaging techniques are promising, radiation exposure (CT), potential adverse events due to contrast (CT/MRI), limited access (MRI), high cost (MRI), and inability to scan at the bedside or in operating theater are disadvantages of the conventional techniques.10 To address these shortcomings, various imaging techniques, including optical imaging, have been explored for tissue perfusion imaging.11, 12 In optical imaging, the optical contrast of tissues is intrinsically sensitive to tissue abnormalities, such as changes in oxygenation, blood concentration or scattering.13, 14 These changes are characteristic of many tumors, since they include angiogenesis, hypervascularization, hypermetabolism, and hypoxia, making optical imaging techniques promising candidates for perfusion imaging in oncology.
Hyperspectral imaging (HSI) is an emerging optical imaging technique that uses light to obtain information about perfusion, or more specifically about oxygenation, water content or hemoglobin content of the tissue. The distinct advantage of HSI is that it is a noncontact, nonionizing, and noninvasive modality and does not require a contrast agent. HSI integrates conventional imaging and spectroscopy techniques by creating a set of images called a hypercube, which contains the spectral signature of the underlying tissue and in turn points to clinically relevant changes, such as angiogenesis or hypermetabolism. Figure 1 illustrates the structure and composition of hyperspectral images and physiological parameters derived from these images.
Structure and composition of hyperspectral images and physiological parameters derived from the images, which are typically displayed in false color.
NIR PI = near-infrared perfusion index; OHI = organ hemoglobin index; StO2 = oxygen saturation of tissue; TWI = tissue water index
HSI was originally employed in remote sensing applications16, 17 and then expanded into other fields, such as vegetation type and water source detection18, 19, wood product control20, drug analysis21, food quality control22-25, artwork authenticity and restoration26, 27, and security28. HSI is also an attractive modality in the medical field and has been successfully applied for the detection of various types of tumors, particularly in conjunction with histopathologic diagnosis.29-31 HSI has,
How valuable HSI could be in quantifying perfusion changes during interventions in clinical oncology remains unclear, and to that end, we decided to systematically review the literature with the intention of exclusively focusing only on studies in which HSI was performed on patients in the clinical oncology setting.
Two authors (R.H. and M.M.) conducted jointly – to preclude potential bias – a comprehensive literature search on October 3, 2022 through PubMed and Web of Science electronic databases using the following search terms: »hyperspectral imaging perfusion cancer« and »hyperspectral imaging resection cancer«. No restrictions in publication date or language were imposed. The inclusion criterion was the application of the hyperspectral imaging modality in the oncological clinical setting, meaning that all animal and phantom,
A flow diagram of the selection strategy is shown in Figure 2; in total, 101 and 84 articles were found to be of interest in the PubMed and Web of Science databases, respectively. After excluding duplicates and applying the exclusion criteria, first considering the title and abstract, and next, if necessary, reading the entire article, 20 articles were identified for further analysis. The anatomical locations of tumors in the selected articles were as follows: kidneys (1 article), breasts (2 articles), eye (1 article), brain (4 articles), entire gastrointestinal (GI) tract (1 article), upper GI tract (5 articles) and lower GI tract (6 articles).
Flow diagram of the selection strategy.
Taken from Pfahl
Pioneering effort in assessing perfusion by means of HSI in clinical oncology was the work of Best
Images of the kidney depicting the percentage of HbO2 as a function of color. A dark red represents high values while the yellows and greens indicate lower values.
Taken from Best
Included articles reporting the use of hyperspectral imaging (HSI) to quantify perfusion changes in clinical applications in oncology
Reference | Year of publication | Number of patients | Oncologic intervention | System | Algorithm |
---|---|---|---|---|---|
Best34 |
2013 | 26 | Partial nephrectomy | DLP HSI, 520–645 nm | Supervised multivariate least squares regression |
Rose35 |
2018 | 8 | Radiation retinopathy | Tunable laser, 520–620 nm with 5 nm steps | PHYSPEC software (Photon etc., Montreal, QC, Canada) |
Chin36 | 2017 | 43 | Skin response to radiation | OxyVu-2TM (Hypermed, Inc., Waltham, MA), 500–600 nm | The OxyVu-2TM software (Hypermed, Inc., Waltham, MA) |
Pruimboom8 | 2022 | 10 | Mastectomy skin flap necrosis | TIVITA™ (Diaspective Vision GmbH, Am Salzhaff, Germany), 500– 1000 nm with 5 nm step | TIVITA™ (Diaspective Vision GmbH, Am Salzhaff, Germany) |
Fabelo37 | 2018 | 22 | Craniotomy for resection of intraaxial brain tumor | Hyperspec VNIR A-Series (HeadWall Photonics, Massachusetts, USA), 400–1000 nm | Spectral angle mapper |
Fabelo38 | 2018 | 5 | Craniotomy for resection of intraaxial brain tumor; all 5 patients with grade IV glioblastoma | As in Fabelo37 | As in Fabelo37 |
Fabelo39 | 2019 | 6 | Craniotomy for resection of intra-axial brain tumor; all 6 patients with grade IV glioblastoma | As in Fabelo37 | As in Fabelo37 |
Fabelo40 | 2019 | 22 | Craniotomy for resection of intraaxial brain tumor | As in Fabelo37 | As in Fabelo37 |
Jansen-Winkeln41 [Article in German] | 2018 | 47 | Gastrointestinal surgery with esophageal, gastric, pancreatic, small bowel or colorectal anastomoses | As in Pruimboom8 | As in Pruimboom8 |
Kohler9 | 2019 | 22 | Hybrid or open esophagectomy followed by reconstruction of gastric conduit | As in Pruimboom8 | As in Pruimboom8 |
Moulla42 [Article in German] | 2020 | Video presentation of hybrid esophagectomy | As in Pruimboom8 | As in Pruimboom8 | |
Schwandner43 | 2020 | 4 | Hybrid esophagectomy followed by reconstructing gastric conduit | As in Pruimboom8 | As in Pruimboom8 |
Hennig44 | 2021 | 13 | Hybrid esophagectomy followed by reconstructing gastric conduit | As in Pruimboom8 | As in Pruimboom8 |
Moulla45 | 2021 | 20 | Pancreatoduodenectomy | As in Pruimboom8 | As in Pruimboom8 |
Jansen-Winkeln46 | 2019 | 24 | Colorectal resection | As in Pruimboom8 | As in Pruimboom8 |
Jansen-Winkeln47 | 2020 | 32 | Colorectal resection | As in Pruimboom8 | As in Pruimboom8 |
Pfahl48 | 2022 | 128 | Colorectal resection | As in Pruimboom8 | As in Pruimboom8 |
Jansen-Winkeln49 | 2021 | 54 | Colorectal resection | As in Pruimboom8 | As in Pruimboom8 |
Jansen-Winkeln50 | 2022 | 115 | Colorectal resection | As in Pruimboom8 | As in Pruimboom8 |
Barberio51 | 2022 | 52 | Colorectal resection | As in Pruimboom8 | As in Pruimboom8 |
GI = gastrointestinal
Taken from Fabelo
In the study of Rose
Chin
Pruimboom
Fabelo
In their first methodological paper, they designed a special cancer detection algorithm utilizing spatial and spectral features of hyperspectral images from 5 patients with grade IV glioblastoma.38 They demonstrated that it was possible to accurately discriminate between normal tissue, tumor tissue, blood vessels and background by generating classification and segmentation maps in surgical time during neurosurgical operations, as shown in Figure 4.
In their second methodological paper39, they used data from 6 patients with grade IV glioblastoma and applied improved algorithms to create maps, in which the parenchymal area of the brain could be delineated; an overall average accuracy of 80% was achieved.
Their HSI system was systematically assessed at two clinical institutions enrolling 22 patients, and researchers found that results relevant for surgeons were obtained within 15 to 70 seconds.40 They also made available to the public this first
HSI files from the studies by Fabelo and co-workers are available from
During the past 3 years, the main focus of applying HSI in clinical oncology has been in the domain of the gastrointestinal tract, or more specifically, addressing anastomotic insufficiency, which is one of the most serious postsurgery complications of reconstructing the gastrointestinal conduit. As anastomotic healing fundamentally depends on adequate perfusion, HSI could be a suitable modality in assessing anastomotic perfusion in clinical practice. In a pilot study, Jansen-Winkeln
Köhler
Comparison of Red-Green-Blue (RGB) images and near-infrared perfusion index (NIR PI) images recorded in a patient with
Taken from Köhler
Hennig
Moulla
Hyperspectral imaging (HSI) acquisition system in the operating room. Hyperspectral images were acquired within a few seconds with physiologic HSI parameters displayed in false colors.
Taken from Moulla
Jansen-Winkeln
Jansen-Winkeln
In another study49, Jansen-Winkeln
Usefulness of hyperspectral imaging (HSI) in establishing transection line during colorectal surgery. The Red-Green-Blue (RGB) image
Taken from Barberio
Based on this literature review, the following inferences could be made: HSI is still finding its place in oncological clinical applications with the assessment of (i) mastectomy skin flap perfusion after breast reconstructive surgery8 and (ii) anastomotic perfusion during reconstruction of gastrointenstinal conduit9,44,45,48-50 as the most promising. However, caution needs to be advised because recently much research has been done in the arena of using HSI during brain surgery for glioblastoma, yet this clinical effort has not been sustained.
In addition, the need for an obvious expansion of the study of Pruimboom
When evaluating applications of HSI in assessing anastomotic perfusion during reconstructing gastrointestinal conduits, two main challenges become apparent: (i) the first challenge is, as in the case of breast reconstructive surgery, related to the establishment of a clear cutoff value indicating adequate tissue perfusion so that the operator can convincingly identify the optimal anastomosis area; (ii) the second challenge is related to HSI being limited to open surgery due to the large size of the HSI camera. The first challenge will need to be approached by enrolling progressively larger patient groups undergoing various oncological surgical interventions. It appears that the group of Jansen-Winkeln
Comparison of HSI and FI-ICG44, 47, 48 revealed similar results in defining the perfusion border of anastomosis, while both modalities were documented to be reliable, fast, and intuitive. Even if HSI is completely noninvasive, injection of ICG rarely provokes allergic reactions. Since there is a potential for each of the two modalities to contribute complementary information, it is not surprising that Pfahl
In conclusion, HSI is at this stage emerging as an attractive imaging modality to quantify perfusion in oncological patients. Hopefully, a larger number of clinical sites will initiate clinical trials to address the challenges, which still preclude the final acceptance of this promising imaging technique in the oncological clinical setting.