PCa, a 3-month follow-up exam is warranted. Once the cancer shows signs of regressing, based primarily on measures of vascularity and density, a 6 to 9-month follow-up schedule is more appropriate. MRIs should be repeated when the tumor has not responded to treatment by 6-months. Routine ultrasound follow up should be on a 6-month basis and MRI yearly for 3-years.
•Tumor size alone can be misleading: The routine use of tumor size decrease has been shown to be less reliable than blood flow analysis, since the edema of cell death may cause dying cancers to enlarge. Although this concept was described in the early 1990’s in Europe, it was first mentioned in the American literature in 1996 at the American Roentgen Ray Society Annual Meeting. Dr. E. Louvar from the Henry Ford Hospital combined radiology and pathology studies to determine that the power Doppler flows in malignancies was related to the vessels that fed aggressive tumors.
•Highly correlated to Gleason scores: Significantly higher Gleason scores were seen in cancer biopsies of high Doppler flow areas compared to cancers with no Doppler flows. Dr. D. Downey at John Robarts Research Institute of the University Hospital in Ontario, Canada has looked at vascular imaging techniques and 3-D imaging of blood vessels. Blood vessels can be rendered in 3-D with angiography (high intensity dye injected into arteries), CT scanning (medium intensity dye), MR angiography (low intensity dye), 3-D color Doppler imaging, and 3-D power Doppler imaging. In this article, published from the American Journal of Radiology in 1995, he noted that in PCa power Doppler was better able to delineate the abnormal vessel architecture than color Doppler techniques. Indeed, computer analysis of malignant vessel density is now being used as a substitute for Gleason grading, which is solely based on randomly obtained histologic microscopic findings.
Clinical Advantage of Doppler Technologies
•Treatment alters standard diagnostic accuracy: A 2004 newsletter from the Prostate Cancer Research Institute reported that hormone therapy may change the way the pathologist interprets a cancer. Androgen deprivation therapy, (ADT) and similar medicines such as Proscar (finasteride), Avodart (dutasteride) and certain hair maintenance formulations, make it more difficult to grade the tumor with microscopic analysis. Dr. Pam Unger, a PCa pathology specialist at Mount Sinai Hospital in New York, mentioned in a personal communication that radiation changes also caused difficulties in reading the microscopic slides. Furthermore, pathologists generally don’t look for blood vessels, and thus, do not routinely evaluate the vascular pattern in the specimens they interpret.
•Blood flow, measured by Doppler sonogram, is not disrupted by treatments: The diagnostic accuracy of 3-D Doppler, based on blood flow analysis, is not altered by the treatments noted above. Men who have been on ADT should have a Doppler sonogram study to confirm the absence of residual disease. If there are areas of abnormal blood vessels, biopsy may be considered. Many patients who have been treated for cancer accept the presence of abnormal blood flows as proof of recurrence and choose treatments accordingly without further biopsies. Most patients use the amount of decrease in number of the visible blood vessels to represent the degree of success.
MRI Complements Doppler Imaging of the Prostate
There are several MRI formats for examining the prostate. Each has its own characteristics and can refine the diagnosis. MRI routinely refers to the image of signal intensity in the gland with the patient in the tube of the unit. Three primary MRI formats have proven useful for prostate examination: EC-MRI uses an endorectal coil (EC) to improve resolution in the prostate; S-MRI (spectroscopic-MRI) involves analysis of the chemical composition of the prostate tissues, with emphasis on the compound choline; DCE-MRI (dynamic contrast enhanced-MRI) is the most useful format to complement 3-D Doppler for a complete diagnosis. DCE-MRI uses the injection of a contrast agent (gadolinium) that reveals the blood flow within tumorous prostatic tissue.4
MRI shows cancer as a loss or decrease of the normal glandular prostatic tissue signal, however, other benign pathologies, such as calculi, hemorrhage (bleeding from recent biopsy), stones, benign prostatic hyperplasia (BPH), and inflammation, may also produce this effect. Some infiltrating types of cancer will not produce any visible changes. The data from the 2009 American Roentgen Ray Meeting shows a 75% sensitivity (25% false negatives) and 95% specificity (5% false positives). MRI was originally used to stage the spread of cancer outside the prostate gland also denoted as ECE (extra capsular extension). The data showed ECE medium specificity (74%) and sensitivity (71%).
Each MRI format has a unique purpose:
•EC-MRI: By using the endorectal coil inflated as a balloon, EC-MRI was designed to better define the capsule of the gland and the seminal vesicles.
•S-MRI: This format was designed to detect intraglandular cancer and shows the aggression. The spectroscopic chemical analysis of cancer shows higher levels of choline and citrate than in normal prostatic tissues. The analyzed sections of the prostate are divided into a grid pattern of such a size that small cancers could be missed. While this technique appeared useful for larger tumors, a 2010 article noted an overall sensitivity of 56% for tumor detection. Currently, S-MRI is practiced at few medical centers in the US and is losing popularity at many international academic facilities. A 2008 presentation by Dr. O. Rouviere from Lyon, France at the French Radiology Meeting highlighted the problem that S-MRI was not effective in analyzing tumor extension into the fatty tissues adjacent to the prostate gland.
•DCE-MRI: This format is widely used and has improved specificity by about 80% according to the 2008 RADIOLOGY article by Drs. J. Futterer and J. Barentsz and sponsored by the Dutch Cancer Society. DCE-MRI provides noninvasive analysis of prostate vascularization as well as tumor angiogenesis and capillary permeability characteristics in PCa's. (This group has also developed a 3-D S-MRI system that improves the overall accuracy of standard S-MRI.)
A fourth MRI type takes a different approach:
•DWI-MRI: DWI-MRI (diffusion weighting imaging-MRI) is a process that shows molecular motion inside a tumor. The more motion, the more likely a lesion is benign, as in a fluid filled cyst. Several articles now assert that this technology may be used to predict Gleason scores.
Comparing Doppler and MRI
An MRI exam shows the extent of cancer but not the activity. In patients successfully treated by radiation or hormones, the abnormality may still persist on the MRI picture; whereas, the Doppler test has the advantage of showing that blood flows are greatly reduced or completely absent. S-MRI is also designed to show activity, but has not been shown to be as sensitive as physicians had hoped. DWI- MRI has not been successful in finding small lesions and EC-MRI has been shown to distort the anatomy by the balloon inflation process. Most MRI fails to show small areas of extracapsular disease. Fortunately, the latest generation of 3D 18 MHz ultrasound probes have a resolution 5-times greater than the MRI and can verify capsule integrity. MRI is used to find spread of the prostate tumor into the boney structures, seminal vesicles, and lymph nodes. It may also confirm extension of malignancy into the rectum.
Working With 3-D Doppler Imaging
The ultrasonographic physician or specially trained imaging technician looks at the instantaneous video appearing on the screen, taking pictures and measuring images according to a standard protocol, and notes and documents abnormalities. Two dimensional pictures are taken in “real time,” which are similar to the images of the inside the pregnant mother’s womb showing moving babies or the fetal heart beating. The same 3-D technology that shows the face of the baby in the womb is now being successfully applied to the prostate. 3-D is different, in that it is faster, yet contains more information than the standard 2-D sonogram.
3-D Data Analysis
Essentially,
