WEST LAFAYETTE, Ind. \u2014 Like each person, each cancer is unique. And with the growing array of chemotherapy drugs available, gaining early insight into how individual tumors respond to specific drugs would help improve treatment. Harnessing the tools of laser light, the Doppler effect and AI, Purdue University scientist David Nolte is building an imaging system to do just that.<\/p>\n\n\n\n
Nolte\u2019s goal is to personalize and improve chemotherapy treatment. In a project launched this spring that will test its capabilities, the system is being used to assess experimental chemotherapy drugs for osteosarcoma, a common and often serious bone cancer. The unique data the system gathers will one day pinpoint the best drugs for the individual tumor, shortening the costly, time-consuming pipeline that stands between a lab bench and a patient in need.<\/p>\n\n\n\n
Nolte, the Edward M. Purcell Distinguished Professor of Physics and Astronomy and a member of the Purdue Institute for Cancer Research<\/a>, hopes the system will be used for a rapid evaluation of patient biopsies obtained during diagnosis, which will help doctors choose the most effective chemotherapy for each patient. He envisions a wide variety of uses for his \u201cbiodynamic imaging\u201d system in healthcare and life sciences.<\/p>\n\n\n\n \u201cAll living systems are basically little machines, and cancer drugs affect how those machines run. This means that some things move faster in some parts and slow down in others, and we can see those changes,\u201d Nolte said. \u201cWe can use motion as a form of image contrast in light imaging. My optical technique is general and has opened all kinds of applications.\u201d<\/p>\n\n\n\n Nolte recently installed a prototype in the lab of Karen Pollok, professor of pediatrics at Indiana University School of Medicine. There, Pollok will use Nolte\u2019s equipment to evaluate the impact of experimental chemotherapy drugs on tumor cells derived from more than 30 osteosarcoma patients, including a cell line donated by Tyler Trent<\/a>, a beloved Purdue student who succumbed to osteosarcoma in 2019. In studying multiple cell lines simultaneously, the team can conduct broad testing, running every drug and drug combination with the potential to benefit patients. Pollok\u2019s patient-derived models are a carefully characterized resource that captures the key genetic drivers of each patient\u2019s cancer, and they can serve as a reference atlas to inform work with new patients.<\/p>\n\n\n\n To understand the meaning of changes the imaging system captures, Nolte trains AI algorithms on images with known outcomes, the same way now-ubiquitous image recognition programs are trained. Once calibrated, the system will be able to predict outcomes from new images.<\/p>\n\n\n\n \u201cOne of the challenges in developing new cancer therapies is understanding, as early as possible, how a tumor is responding to a potential treatment,\u201d Pollok said. \u201cIt\u2019s especially meaningful to apply this technology to living 3D tissue derived from Tyler Trent\u2019s tumor, along with models from many other osteosarcoma patients who are part of this effort. We hope it will give us new insight into how these tumors respond to experimental drugs and, over time, help us more quickly identify the treatments that warrant further study.\u201d<\/p>\n\n\n\n In earlier work with a team of researchers, Nolte tested this approach against drug and tumor reactions researchers already understood from more traditional research \u2014 in what is known as a retrospective clinical trial \u2014 for muscle-invasive bladder cancer patients undergoing neoadjuvant chemotherapy, a common but not universal treatment for the disease. Their study<\/a>, published in 2023, accurately predicted whether patients at four bladder cancer centers would benefit from the therapy, a promising indication that biodynamic imaging can provide a fast and simple quantitative analysis that can help doctors choose the most effective course of treatment.<\/p>\n\n\n\n The system was successfully used at IU School of Medicine in a Phase II clinical trial <\/a>to predict chemoresistance in human esophageal carcinoma, and it was also used in a preclinical trial<\/a> of canine B-cell lymphoma at Purdue. In other current projects, biodynamic imaging is being used to predict the viability of in vitro fertilized livestock embryos<\/a> and to spot bacterial and viral infections<\/a>.<\/p>\n\n\n\n Work on the imaging system is supported by the National Science Foundation\u2019s Chemical, Bioengineering, Energy and Transport Systems division, and by a pilot award from the National Center for Advancing Translational Sciences\u2019 Clinical and Translational Science Awards, which is supported by the National Institutes of Health.<\/p>\n\n\n\n Nolte, a 2025 National Academy of Inventors fellow<\/a>, disclosed his innovation to the Purdue Office of Technology Commercialization<\/a> and was recently awarded a patent on an improved version of his system<\/a> that renders the system far more user-friendly. His hope is that his system will someday be tested in a prospective clinical trial to determine which of two common courses of breast cancer therapy \u2014 Adriamycin\/Cytoxan (AC) and Taxotere\/Cytoxan (TC) \u2014 would be most effective for a patient, a decision that is now largely dependent on where patients are treated.<\/p>\n\n\n\n \u201cWithin 48 hours of a patient having a biopsy removed, we could tell the doctor, \u2018This patient will respond better to AC than to TC,\u2019 or vice versa,\u201d Nolte said. \u201cIf we were successful with a prospective trial, we could change the standards of care in the United States.\u201d <\/p>\n\n\n\n The novelty of the system is the combination of laser light with the Doppler effect \u2014 the stretching and pulling of electromagnetic waves familiar to anyone who has heard the change in pitch of a speeding motorcycle as it passes by. When bounced off a moving target, any wavelength of light will exhibit the Doppler effect, stretching or compressing depending on whether the target is moving toward or away from the source of light. But laser light offers unparalleled sensitivity to movement.<\/p>\n\n\n\n To understand why, Nolte says it\u2019s helpful to think of laser light \u2014 which exhibits properties of both a particle and a wave \u2014 as a pulse of a wavelength, a little snippet of a wave with a set beginning and end. Ordinary white light is a hodgepodge, with pulses of different-sized waves emanating from the source in staggered series. But the pulses in laser light are organized, moving forward like a marching band, aligned in a fixed, predictable order that physicists call coherence. Because many pulses reach the object and report back \u2014 either compressed or stretched \u2014 simultaneously, Nolte estimates laser light offers roughly 1 million times greater sensitivity to movement than the best light microscope. <\/p>\n\n\n\n Nolte\u2019s system detects infinitesimal motion of cellular machinery within living tissue that is imperceptible to conventional medical imaging like microscopy, X-ray or MRI. By observing living movement at the nanometer scale, he gains a front-row seat to cellular mechanisms as they unfold. When the biodynamic images are analyzed with AI, those nascent events are translated into predicted outcomes.<\/p>\n\n\n\n \u201cIn my lab we track how everything inside of living cells is moving,\u201d Nolte said. \u201cLet\u2019s say something inside of a living cell is moving at a speed of about the diameter of one hydrogen atom per second. You could not measure that movement with any kind of ordinary light. But we can. We are picking up average motions down to about 30 picometers per second.\u201d<\/p>\n\n\n\n Purdue University is a research institution ranked among the top 10 public universities in the United States. More than 111,000 students study at Purdue across multiple campuses, including more than 57,000 at our main campus locations in West Lafayette and Indianapolis. As a land-grant university committed to affordability and accessibility, Purdue\u2019s main campus has frozen tuition 14 years in a row, enabling more students than ever to graduate debt-free.<\/p>\n\n\n\n Biodynamic prediction of neoadjuvant chemotherapy response: Results from a prospective multicenter study of predictive accuracy among muscle-invasive bladder cancer patients<\/em> Comparative oncology chemosensitivity assay for personalized medicine using low-coherence digital holography of dynamic light scattering from cancer biopsies<\/em> Biodynamic digital holography of chemoresistance in a pre-clinical trial of canine B-cell lymphoma<\/em> Biodynamic digital holographic speckle microscopy for oocyte and embryo metabolic evaluation<\/em>Exponentially greater sensitivity to the movement of living tissue<\/h2>\n\n\n\n
About Purdue University<\/h2>\n\n\n\n
Papers<\/h2>\n\n\n\n
Urologic Oncology: Seminars and Original Investigations
DOI: 10.1016\/j.urolonc.2022.11.017<\/a><\/p>\n\n\n\n
Scientific Reports
DOI: 10.1038\/s41598-024-52404-w<\/a><\/p>\n\n\n\n
Biomedical Optics Express
DOI: 10.1364\/BOE.9.002214<\/a><\/p>\n\n\n\n
Applied Optics
DOI: 10.1364\/AO.404298<\/a><\/p>\n\n\n\n