New Noninvasive Gold Standard for PCa Diagnosis: An Interview With Vikram Dogra, MD

A nascent technology known as multispectral photoacoustic imaging (PA imaging) combines laser optics and ultrasound to distinguish between benign and malignant prostate tissue. 

Diagnostic radiologist Vikram S. Dogra, MD, a professor of imaging sciences, urology, and biomedical engineering at the University of Rochester Medical Center School of Medicine & Dentistry in Rochester, N.Y., helped develop this less expensive and noninvasive alternative to transrectal ultrasound (TRUS)-guided prostate biopsy in collaboration with  Naval Rao, PhD, of the  Rochester Institute of Technology.

How did you and your team come to develop PA imaging?

Dr. Dogra: It was in 2007-2008 that we wanted to come up with a novel approach to diagnose cancer. Being a radiologist, I am very familiar with limitations of all imaging modalities that are used to detect cancer. The main problem today is that most imaging is binary—a lesion either does or does not enhance on imaging, and that may be hypo- or hyperechoic-relative to the lesion's surroundings. Based on this limited information it's not possible to make a diagnosis of cancer, but that's what we have been doing. Moreover, these are anatomical studies and not functional.

Today's imaging is not always helpful in the assessment of treatment efficacy?

Dr. Dogra: Most of the time, we go by the size of the lesion: “The lesion was 2 cm before. After treatment, did it reduce in size or not?”

Not all lesions reduce in size, but that does not mean they did not respond to therapy. Current imaging modalities mainly identify reduction in the size of the tumor; therefore, they do not reflect true efficacy of cancer treatment. But we can only measure the size; we cannot measure any other thing that has happened to or in the lesion. So we are just stuck. If the outcome was simply related to size, then we'd be very happy, but unfortunately it is not.

Intrigued by these problems, we came up with the idea of lens-based, low-cost photoacoustic imaging. This imaging is noninvasive and non-radiation-based, and most important, it is functional. That is, it is based on the chemical composition of the tumor, such as deoxyhemoglobin, oxyhemoglobin, water, and lipid content.

How is that information relevant?

Dr. Dogra: Many specific chemicals and enzymes can be studied in a given tumor to allow for diagnosis. We can tell if prostate tissue is malignant or benign by observing increases and decreases in deoxyhemoglobin, oxyhemoblobin, water, and lipids, and PA imaging allows us to make those observations.

Our results with PA imaging show significant differences in optical absorption values of hemoglobin (Hb), whole blood, oxyhemoglobin (HbO2), and water between normal and malignant tissue. Similarly, there are differences in optical absorption values of Hb, HbO2, and lipid between benign prostatic hyperplasia (BPH) and malignant tissue. The difference between optical absorption of water in normal tissue compared with BPH tissue was also significant.

PA imaging can be used for prognosis as well as for diagnosis. An increase or decrease in the particular molecule being treated and measured can indicate response to treatment.

How does PA imaging actually work?

Dr. Dogra: Photoacoustic (PA) signal is generated in tissue in response to low-energy nanosecond pulses of laser light, administered at FDA-approved levels, usually in the near-infrared region. The absorption of a short optical pulse causes localized heating and rapid thermal expansion, which generates thermoelastic stress waves, or ultrasound waves. These ultrasound waves, referred to as PA waves, are generated instantaneously and simultaneously everywhere in a three-dimensional tissue volume irradiated by the laser pulse.

The PA signal amplitude is proportional to the optical absorption of laser intensity by the absorber, and PA images are gathered by mapping the location and strengths of the absorbers in the tissue.