Adeniyi Adedeji Ahmed, Adeshina Adetunji Steve, Muhammad Aliyu Suleiman, Aleshinloye Yusuf Abass
Abstract
The utilization of computer-aided diagnosis (CAD) systems based on deep learning technologies for histopathology images analysis and cancer detection has been highly successful. However, many of these techniques make use of regular Red-Green-Blue (RGB) whole slide images, which offers only limited spectral data for precise tissue characterization, making it difficult for the model to recognize pathological features in biological tissues. This ultimately pushes RGB-based histopathology systems gradually towards an information bottleneck, given the increasing demand for higher diagnostic precision and early disease detection. In this regard, Hyperspectral imaging (HSI) can be considered as an alternative imaging method, allowing comprehensive spectral-spatial information obtained from multiple wavelength bands, thereby improving tissue analysis capabilities and disease detection. Recently, HSI have earned increased attention in computational pathology due to its capability to increase diagnostic accuracy compared to the conventional RGB imaging technology. This paper presents a review of Hyperspectral imaging in computer- aided histopathology diagnosis. The study examines the basics of hyperspectral imaging HSI, deep learning approaches in HSI, publicly available data sets, advantages of HSI in comparison to conventional RGB- based systems, and current challenges in HSI development along with possible avenues of further investigation. The review reveals that hyperspectral imaging possesses significant potential for advancing next-level digital pathology and precision diagnostic applications.
Keywords
Hyperspectral Imaging, Histopathology, Computer-Aided Diagnosis, Deep Learning, Spectral- Spatial Learning, Whole Slide Imaging, Medical Imaging, Artificial intelligence.
Conclusion
Hyperspectral imaging technique is becoming more popular in the field of computer-aided histopathology diagnosis, owing to the capability of the technique to provide both spectral and spatial information regarding the tissue [25]. In contrast to conventional imaging systems which focus mainly on the structural details of the tissues, HSI is able to generate biochemical and spectral features that improve the process of tissue classification and discrimination [26], [34]. AI techniques such as deep learning, spectral-spatial convolutional neural networks, transformers, and self-supervised learning have recently revolutionized HSI-based computer-aided diagnostic systems [36], [33], [37]. However, despite all these improvements, there are still many obstacles that prevent the implementation of such HSI systems in a clinic, which include issues of high-dimensionality, inadequate benchmark datasets, difficulties with data annotation, computational power demands, non-standard acquisition protocols, and integration into clinical workflow [45], [46]. Despite these problems, research is still actively being conducted into such fields as explainable AI, federated learning, multimodal imaging, lightweight transformer models, and foundation models for hyperspectral pathology [6], [59] [49]. It is highly probable that future computational pathology systems will combine hyperspectral imaging with multimodal AI models that can utilize spectral, morphological, genomic, and clinical data in order to achieve better precision medicine [63]. Therefore, hyperspectral imaging shows great potential for revolutionizing the field of digital pathology and next-generation AI-based cancer diagnostics.
References
[1]I. Ahmad and F. Alqurashi, “Early cancer detection using deep learning and medical imaging: A survey,” Critical Reviews in Oncology/Hematology, vol. 204, p. 104528, 2024.
[2]R. L. Siegel, A. N. Giaquinto and A. Jemal, “Cancer statistics, 2024.,” CA Cancer J Clin, vol. 74, no. 1, 2024.
[3]F. Bray, M. Laversanne, H. Sung, J. Ferlay, R. L. Siegel,
I. Soerjomataram and A. Jemsl, “Global cancer statistics 2022: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries.,” CA Cancer J Clin, vol. 74, no. 3, p. 229, 2024.
[4]M. Imran, I. Shafi and J. Ahmad, “Virtual histopathology methods in medical imaging – a systematic review.,” BMC Med Imaging, vol. 24, no. 318, 2024.
[5]S. Aishima, Y. Kubo, Y. Tanaka and Y. Oda, “Pathological features and prognosis of combined hepatocellular and cholangiocarcinoma by world health organization classification.,” in LABORATORY INVESTIGATION, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA, NATURE PUBLISHING GROUP, 2013, pp. (Vol. 93, pp. 396A- 397A).
[6]S. C. Huang, A. Pareek, M. Jensen, M. P. Lungren, S. Yeung and A. S. Chaudhari, “Self-supervised learning for medical image classification: a systematic review and implementation guidelines.,” NPJ Digital Medcine, vol. 6, no. 1, p. 74, 2023.
[7]”Trend in radiologist workload compared to number of admissions in the emergency department.,” European Journal of Radiology , vol. 149, p. 110195, 2022.
[8]J. L. Alonso-Martínez, F. A. Sanchez and M. U. Echezarreta, “Delay and misdiagnosis in sub-massive and non-massive acute pulmonary embolism,” European journal of internal medicine, vol. 21, no. 4,
pp. 278-282, 2010.
[9]”Clinical characteristics associated with diagnostic delay of pulmonary embolism in primary care: a retrospective observational study.,” BMJ open, vol. 7, no. 3, p. e012789, 2017.
[10]A. Esteva, J. Feng, D. Van der WAl, S. C. Huang, J. P. Simko, S. DeVries, E. Chen, E. M. Schaeffer, T. M. Morgan, Y. Sun and A. Ghorbani, “Prostate cancer therapy personalization via multi-modal deep learning on randomized phase III clinical trials.,” NPJ digital medicine, vol. 5, no. 1, p. 71, 2022.
[11]A. Esteva, J. Feng, S. C. Huang, D. Van Der Wal, J. Simko, S. Devries, E. Chen, E. M. Schaeffer, T. M. Morgan, J. M. Monson and F. Naz , “Development and validation of a prognostic AI biomarker using multi- modal deep learning with digital histopathology in localized prostate cancer on NRG Oncology phase III clinical trials.,” J. Clin. Orthod., vol. 40, pp. 222-222, 2022.
[12]”Deep learning–assisted diagnosis of cerebral aneurysms using the HeadXNet model,” JAMA network open, vol. 2, no. 6, pp. e195600-e195600, 2019.
[13]”Deep-learning-assisted diagnosis for knee magnetic resonance imaging: development and retrospective validation of MRNet.,” PLoS medicine, vol. 15, no. 11,
p. e1002699, 2018.
[14]”Performance of a Deep-Learning Neural Network Model in Assessing Skeletal Maturity on Pediatric Hand Radiographs,” Radiology, vol. 287, pp. 313-322, 2018.
[15]A. Esteva, B. Kuprel, R. A. Novoa, J. Ko, S. M. Swetter,
H. M. Blau and S. Thrun, “Dermatologist-level classification of skin cancer with deep neural,” Nature, vol. 542, no. 7639, pp. 115-118, 2017.
[16]L. He, L. Rodney Long, S. Antani and G. Thoma, “Histology image analysis for carcinoma detection and grading,” Computer Methods and Programs in Biomedicine, vol. 107, no. 3, pp. 538-556, 2012.
[17]K. Wakizaka, H. Yokoo, T. Kamiyama, M. Ohira, K. Kato, Y. Fujii, K. Sugiyama, N. Okada, T. Ohata, A. Nagatsu, S. Shimada, T. Orimo, H. Kamachi and A. Taketomi, “Clinical and pathological features of combined hepatocellular-cholangiocarcinoma compared with other liver cancers,” J. Gastroenterol. Hepatol, vol. 34, pp. 1074-1080, 2019.
[18]G. Litjens, P. Bandi, B. bejnordi, O. Geessink, M. Balkenhol, P. Bult, A. Halilovic, M. Hermsen, R. van de Loo, R. Vogels, Q. Manson, N. Stathonikos and A. Baidoshvili, “1399 H&E-stained sentinel lymph node sections of breast cancer patients: the CAMELYON dataset,” GigaScience, vol. 7, no. 6, pp. 1-8, 2018.
[19]A. Tauqeer, A. Asif and A. Sadeghi-Naini, “Detection, localization, and staging of breast cancer lymph node metastasis in digital pathology whole slide images using selective neighborhood attention-based deep learning.,” Sci Rep, vol. 15, p. 37847, 2025.
[20]T. Ding, S. J. Wanger and A. H. Song, “A multimodal whole-slide foundation model for pathology.,” Nat Med, vol. 31, pp. 3749-3761, 2025.
[21]S. Ortega, M. Halicek, H. Fabelo, G. Marrero Callico and B. Fei, “Hyperspectral and multispectral imaging in digital and computational pathology: a systematic review,” Biomedical Optics Express, vol. 11, pp. 3195- 3233, 2020.
[22]S. Li, Z. Mei, L. Qingli, H. Menghan, W. Ying, Z. Jian,
L. Yue and C. Junhao, “Diagnosis of cholangiocarcinoma from microscopic hyperspectral pathological dataset by deep convolution neural networks,” Methods, vol. 202, pp. 22-30, 2022.
[23]H. Pasupuleti, L. Ma, X. Guo and B. Fei, “A spatial- spectral vision transformer model for head and neck cancer detection with hyperspectral, RGB, and synthesized RGB histologic images.,” Proc SPIE Int Soc Opt Eng., 2025.
[24]C. Zhang, C. Xu, Q. Chen, Z. Yu, L. Mou, D. Lei, X. Chen and X. Ma, “HSPath-Bench: A microscopic hyperspectral dataset and local-global learning network for histopathological classification,” Optics & Laser Technology, vol. 194, p. 114413, 2026.
[25]G. Lu and B. Fei, “Medical hyperspectral imaging: a review,” J. Biomed. Opt., vol. 19, no. 1, 2014.
[26]M. Halicek, J. Dormer, J. Little , A. Chen and B. Fei, “Tumor detection of the thyroid and salivary glands using hyperspectral imaging and deep learning.,” Biomed Opt Express, vol. 11, no. 3, pp. 1383-1400,
2020.
[27]G. Saiko, P. Lombardi, Y. Au, D. Queen, D. Armstrong and K. Harding, “Hyperspectral imaging in wound care: A systematic review,” Int Wound J., vol. 17, no. 6, pp. 1840-1856, 2020.
[28]B. Fei, “Hyperspectral imaging in medical applications,” in Data Handling in Science and Technology, vol. 32, Elsevier, 2019, pp. 523-565.
[29]C.-I. Chang, Hyperspectral Imaging: Techniques for Spectral Detection and Classification., Kluwer Academic Publishers, 2003.
[30]M. A. Calin, T. Coman and S. V. Parasca, “Hyperspectral imaging in the medical field: Present and future,” Applied Spectroscopy Reviews, vol. 49, no. 6, pp. 435-
447, 2014.
[31]M. Halicek, H. Fabelo, S. Ortega and J. V. Little, “Hyperspectral imaging for head and neck cancer detection: specular glare and variance of the tumor margin in surgical specimens,” Journal of Medical Imaging, vol. 6, no. 3, p. 035004, 2019.
[32]M. Khan, H. Khan, A. Yousaf, K. Khurshid and A. Abbas, “Modern trends in hyperspectral image analysis: A review,” IEEE Access, vol. 6, pp. 14118-14129, 2018.
[33]H. Wang, X. Zhang and Y. Li, “Attention-guided spectral-spatial convolutional neural networks for hyperspectral histopathology image classification,” Diagnostics, vol. 15, no. 2, p. 344, 2025.
[34]G. Lu, L. Halig, D. Wang, X. Qin and Z. Chen, “Spectral-spatial classification for noninvasive cancer detection using hyperspectral imaging,” Journal of Biomedical Optics, vol. 19, no. 10, p. 106004, 2014.
[35]S. K. Roy, G. Krishna, S. R. Dubey and B. B. Chaudhuri, “HybridSN: Exploring 3D–2D CNN Feature Hierarchy for Hyperspectral Image Classification,” IEEE Geoscience and Remote Sensing Letters, vol. 17, no. 2,
pp. 277-281, 2020.
[36]L. Shen, H. Wang and Y. Liu, “Spectral-spatial transformer networks for hyperspectral medical image analysis,” Biomedical Signal Processing and Control, vol. 96, p. 106640, 2025.
[37]X. Wang, J. Zhao and H. Chen, “Transformer-based hyperspectral image classification for medical imaging applications,” IEEE Access, vol. 12, p. 55871–55885, 2024.Y. Chen, H. Jiang, C. Li, X. Jia and P. Ghamisi, “Deep feature extraction and classification of hyperspectral images based on convolutional neural networks,” IEEE Transactions on Geoscience and Remote Sensing, vol. 54, no. 10, p. 6232–6251, 2016.
[38]H. Fabelo, S. Ortega, R. Lazcano and A. Szolna, “An intraoperative visualization system using hyperspectral imaging to aid in brain tumor delineation,” Sensors, vol. 20, no. 15, p. 4302, 2020.
[39]H. Fabelo, S. Ortega, A. Szolna, D. Bulters and B. Raducanu, “In-Vivo Hyperspectral Human Brain Image Database for Brain Cancer Detection,” IEEE Access, vol. 7, p. 39098–39116, 2019.
[40]M. Garrido, H. Fabelo and S. Ortega, “Hyperspectral imaging for breast cancer diagnosis and classification,” Sensors, vol. 22, no. 3, p. 1023, 2022.
[41]J. Ma, Y. Li and X. Zhang, “Deep spectral-spatial learning for hyperspectral pathology image classification,” Computers in Biology and Medicine, vol. 173, p. 108245, 2024.
[42]B. Geelen, N. Tack and A. Lambrechts, “A compact snapshot multispectral imager with a monolithically integrated per-pixel filter mosaic,” in Advanced Fabrication Technologies for Micro/Nano Optics and Photonics VII, San Francisco, California., 2014.
[43]H. Akbari, L. V. Halig, H. Zhang, Z. G. Chen and A. Y. Chen, “Detection of cancer metastasis using a novel macroscopic hyperspectral method,” Biomedical Optics Express, vol. 3, no. 4, 2012.
[44]J. Li, J. Bioucas-Dias and A. Plaza, “Spectral–Spatial Hyperspectral Image Segmentation Using Subspace Multinomial Logistic Regression and Markov Random Fields,” IEEE Transactions on Geoscience and Remote Sensing, vol. 50, no. 3, pp. 809-823, 2012.
[45]M. E. Paoletti, J. M. Haut, J. Plaza and A. Plaza, “Deep learning classifiers for hyperspectral imaging: A review,” ISPRS Journal of Photogrammetry and Remote Sensing, vol. 158, pp. 279-317, 2019.
[46]S. Li, W. Song, L. Fang and X. Jia, “Deep learning for hyperspectral image classification: An overview,” IEEE Transactions on Geoscience and Remote Sensing, vol. 57, no. 9, pp. 6690-6709, 2019.
[47]The Cancer Genome Atlas Research Network, “The Cancer Genome Atlas Pan-Cancer analysis project.,” Nature Genetics, vol. 45, no. 10, p. 1113–1120, 2013.
[48]M. J. Sheller, B. Edwards, G. A. Reina, J. Martin, S. Pati and A. Kotrotsou, “Federated learning in medicine: facilitating multi-institutional collaborations without sharing patient data,” Scientific Reports, vol. 10, no. 1,
p. 12598, 2020.
[49]M. N. Gurcan, L. E. Boucheron, A. Can and A. Madabhushi, “Histopathological image analysis: a review,” IEEE Reviews in Biomedical Engineering, vol. 2, pp. 147-171, 2009.
[50]D. Komura and S. Ishikawa, “Machine learning methods for histopathological image analysis,” Computational and Structural Biotechnology Journal, vol. 16, pp. 34- 42, 2018.
[51]G. Litjens, T. Kooi, B. Bejnordi, A. Arindra and A. Setio, “A survey on deep learning in medical image analysis,” Medical Image Analysis, vol. 42, pp. 60-88, 2017.
[52]Y. Liu, T. Kohlberger, M. Norouzi, G. Dahl, J. Smith, A. Mohtashamian, N. Olson, L. Peng, J. Hipp and M. Stumpe, “Artificial intelligence-based breast cancer nodal metastasis detection,” Arch. Pathol. Lab. Med., vol. 143, pp. 859-868, 2019.
[53]G. Campanella, M. G. Hanna, L. Geneslaw and A. Miraflor, “Clinical-grade computational pathology using weakly supervised deep learning on whole slide images,” Nature Medicine, vol. 25, no. 8, pp. 1301-1309,
2019.
[54]P. Courtiol, E. Tramel, M. Sansleme and G. Wainrib, “Classification and disease localization in histopathology using only global labels: A weakly- supervised approach,” arXiv preprint arXiv:1802.02212., 2018.
[55]S. Azizi, B. Mustafa, F. Ryan, Z. Beaver and J. Freyberg, “Big self-supervised models advance medical image classification,” in Proceedings of the IEEE/CVF International Conference on Computer Vision (ICCV), Montreal, Canada., 2021.
[56]A. Dosovitskiy, L. Beyer, A. Kolesnikov, D. Weissenborn, X. Zhai and T. Unterthiner, “An image is worth 16×16 words: Transformers for image recognition at scale,” in International Conference on Learning Representations (ICLR), Online, 2021.
[57]W. Hu, Y. Huang, L. Wei, F. Zhang and H. Li, “Deep Convolutional Neural Networks for Hyperspectral Image Classification,” Journal of Sensors, vol. 2015, p. 258619, 2015.
[58]E. Tjoa and C. Guan, “A survey on explainable artificial intelligence (XAI): Toward medical XAI,” IEEE Transactions on Neural Networks and Learning Systems, vol. 32, no. 11, pp. 4793-4813, 2021.
[59]B. Yun, B. Lei, J. Chen, H. Wang, S. Qiu and W. Shen, “SpecTr: Spectral Transformer for Microscopic Hyperspectral Pathology Image Segmentation,” IEEE Transactions on Circuits and Systems for Video Technology, 2025.
[60]H. R. Tizhoosh and L. Pantanowitz, “Artificial intelligence and digital pathology: Challenges and opportunities,” Journal of Pathology Informatics, vol. 9,
p. 38, 2018.
[61]L. Rundo, C. Han and J. Zhang, “CNN and federated learning for medical image analysis: A review,” Computer Methods and Programs in Biomedicine, vol. 204, p. 106113, 2021.
[62]R. J. Chen, M. Y. Lu, D. F. Williamson, T. Y. Chen, J. Lipkova and Z. Noor, “Pan-cancer integrative histology- genomic analysis via multimodal deep learning,” Cancer Cell, vol. 40, no. 8, 2022.R. J. Chen, M. Y. Lu, J. Wang, D. F. Williamson and Lipkova, “Pathomic Fusion: An Integrated Framework for Fusing Histopathology and Genomic Features for Cancer Diagnosis and Prognosis,” IEEE Transactions on Medical Imaging, vol. 41, no. 4, pp. 757-770, 2022.
[63]A. S. Hong, D. Levin, L. Parker, V. M. Rao, D. Ross- Degnan and J. F. Wharam, “Trends in diagnostic imaging utilization among medicare and commercially insured adults from 2003 through 2016.,” Radiology, vol. 294, no. 2, pp. 342-350, 2020.
[64]R. Smith-Bindman, M. L. Kwan, E. C. Marlow, M. K. Theis, W. Bolch, S. Y. Cheng, E. J. Bowles, J. R. Duncan, R. T. Greenlee, L. H. Kushi and J. D. Pole, “Trends in use of medical imaging in US health care systems and in Ontario, Canada, 2000-2016,” Jama, vol. 322, no. 9, pp. 843-856, 2019.
[65]R. J. McDonald, K. M. Schwartz, L. J. Eckel, F. E. Diehn, C. H. Hunt, B. J. Bartholmai, B. J. Erickson and
D. F. Kallmes, “The effects of changes in utilization and technological advancements of cross-sectional imaging on radiologist workload.,” Academic radiology, vol. 22, no. 9, pp. 1191-1198, 2015.
[66]A. Hosny , C. Parmar, J. Quackenbush, L. H. Schwartz and H. J. Aerts, “Artificial intelligence in radiology,” Nature Reviews Cancer, vol. 18, no. 8, pp. 500-510,
2018.
[67]Z. Q. Tang, K. Chuang, C. Decarli, L. Jin, L. Beckett,
M. Keiser and B. Dugger, “Interpretable classification of Alzheimer’s disease pathologies with a convolutional neural network pipeline,” Nature Communications, vol. 10, 2019.
[68]D. Wang, A. Khosla, R. Gargeya, H. Irshad and A. Beck, “Deep Learning for identifying Metastatic Breast Cancer,” arXiv 1606, vol. 05718, pp. 1-8, 2016.
[69]H. Su, F. Liu, Y. Xie, F. Xing, S. Meyyappan and L. Yang, “Region segmentation in histopathological breast cancer images using deep convolutional neural network,” in IEEE 12th international symposium on biomedical imaging (ISBI), 2015.
[70]Y. Bar, I. Diamant, L. Wolf, S. Lieberman, E. Konen and
H. Greenspan, “Chest pathology detection using deep learning with non-medical training,” in 2015 IEEE 12th international symposium on biomedical imaging (ISBI), 2015.
[71]J. Ker, Y. Bai, H. Lee, J. Rao and L. Wang, “Automated brain histology classification using machine learning,”
J. Clin. Neurosci., vol. 66, pp. 239-245, 2019.
[72]L. Sun, M. Zhou, Q. Li, M. Hu, Y. Wen, J. Zhang, Y. Lu and J. Chu, “Diagnosis of cholangiocarcinoma from microscopic hyperspectral pathological dataset by deep convolution neural networks,” Methods, vol. 202, pp. 22-30, 2022.
[73]D. Landgrebe, “Hyperspectral image data analysis.,” IEEE Signal processing magazine, vol. 19, no. 1, pp. 17- 28, 2002.
[74]D. Manolakis, D. Marden and G. Shaw, “Hyperspectral image processing for automatic target detection applications,” Lincoln Laboratory Journal, vol. 14, pp. 79-116, 2003.
[75]M. Ghaffari, A. Chateigner-Boutin, F. Guillon, M. Devaux, H. Abdollahi and L. Duponchel, “Multi- excitation hyperspectral autofluorescence imaging for the exploration of biological samples,” Anal. Chim. Acta, vol. 1062, pp. 47-59, 2019.
[76]N. Dobigeon, J. Tourneret, C. Richard, J. Bermudez, S. McLaughlin and A. Hero, “Nonlinear Unmixing of Hyperspectral Images,” IEEE Signal Process Mag., vol. 31, pp. 82-94, 2014. Q. Li, X. He, Y. Wang, H. Liu, D. Xu and F. Guo, “Review of spectral imaging technology in biomedical engineering: achievements and challenges,” J. Biomed. Opt., p. 100901, 2013.
[77]M. Halicek, H. Fabelo, S. Ortega, G. Callico and B. Fei, “In-Vivo and Ex-Vivo Tissue Analysis through Hyperspectral Imaging Techniques: Revealing the Invisible Features of Cancer,” Cancers, vol. 11, 2019.
How to Cite This Paper
Adeniyi Adedeji Ahmed, Adeshina Adetunji Steve, Muhammad Aliyu Suleiman, Aleshinloye Yusuf Abass (2026). Hyperspectral Imaging for Computer-Aided Histopathology Diagnosis: Opportunities, Challenges, and Future Directions.. International Journal of Computer Techniques, 13(3). ISSN: 2394-2231.