Researchers at the University of California San Diego have developed a new kind of MRI called restriction spectrum imaging (RSI-MRI) that seems to discriminate among Gleason grades 3, 4 and 5 with unmatched geographic precision.
Yamin et al. report on ten prostates that were scanned with RSI-MRI prior to prostatectomy. The prostates were then stained and tumors in them were examined at high resolution. (High resolution, in this study, was 75 micrometers per pixel). In all, 2,795 microscopic “tiles,” grouped to be the size of the MRI voxel, were examined by pathologists and assigned Gleason grades. (An MRI voxel is the minimum volume of matter that can be resolved by an MRI.) They found:
- · RSI-MRI distinguished between cancer and benign tissue
- · RSI-MRI distinguished between Gleason grade 3 and benign tissue
- · RSI-MRI distinguished between Gleason grade 4 and benign tissue
- · RSI-MRI distinguished between Gleason grade 3 and Gleason grade 4
- · It distinguished grades with geographic precision down to the voxel level
In a retrospective evaluation of 33 pre-prostatectomy patients, RSI-MRI was found to more accurately predict prostate cancer and was more highly correlated with Gleason grade. In a similar retrospective evaluation of 28 pre-prostatectomy patients, both RSI-MRI and mpMRI were able to predict the primary Gleason grade across 64 regions of interest. However, RSI-MRI, but not mpMRI, could distinguish primary Gleason grade 3 from 4. In a group of 100 patients with Gleason scores ≥ 4+3, RSI-MRI significantly improved the accuracy compared to mpMRI alone. When combined with only a T2-weighted MRI, it compared favorably to mpMRI.
By comparison, a multiparametric MRI (mpMRI) does a very poor job at distinguishing Gleason grade 3 from benign tissue, and it is geographically much less precise. Even with mpMRI/ultrasound fusion repeat biopsies, known areas of cancer are missed about 30% of the time in men on active surveillance.
It may be a superior tool for staging as well. The same group reported on 27 pre-prostatectomy patients who were staged with MRI and with RSI-MRI. Extraprostatic extension was correctly identified in only 2 of 9 patients (22%) using MRI, but in 8 of 9 patients (89%) using RSI-MRI. It also correctly staged the remaining 18 patients.
To understand this technique, a brief review of multiparametric MRI is in order. Multiparametric MRI, as most commonly used for prostate cancer detection, employs 3 parameters (there are other parameters, like MR Spectroscopy, that are less commonly used):
1. T2 weighting shows areas of different tissue types. Bone, fat, air, calcifications, fibrosis are dark; whereas edema, tumors, and inflammation are light. This shows the basic anatomic detail for the other parameters to be fused with.
2. Dynamic Contrast Enhanced (DCE) MRI uses a gadolinium dye to show areas of blood flow. Tumors often have increased blood supply (called angiogenesis) that does not penetrate well. Because DCE has a relatively low signal-to-noise ratio, features can be difficult to distinguish.
3. Diffusion-Weighted (DWI) MRI shows water circulation in and around cells due to the water molecules’ Brownian (random) motion. Water flows easily around the glandular tissue of a healthy prostate, but as dense tumor cells proliferate, the fluid flow is hindered. These images suffer from spatial distortion, making precise localization for biopsies difficult. Obstacles created by inflammation and necrosis can create false positives.
RSI picks up where DWI leaves off. It detects water molecule motion within the cells. Unlike the hindered motion of water molecules around the outside of cells, cell walls restrict the motion of water molecules within their perimeter. As cancer cells proliferate in the tumor, there is increasing restriction detected. Unlike DWI, RSI does not suffer from spatial distortion and the signal-to-noise ratio is much higher; therefore, tumors stand out in sharper relief. It is unaffected by prostatitis and other tissue anomalies. There is also much less overlap in its ability to distinguish Gleason grades.
Compared to an mpMRI, which takes about an hour, it takes much less time to acquire the images. It is probably less subject to reader error as well. It is easy to see how this can become an important tool in monitoring progression in men on active surveillance, detecting cancer in men where suspicion remains after a first negative biopsy, and in detecting the tumor site for focal therapy and for focal salvage therapy after primary radiation or ablation therapy.
RSI was originally developed to detect and precisely localize brain tumors, and its use for prostate tumor detection is still in its early stages. We will have to have larger prospective trials to validate its use. There is a clinical trial in San Diego, which will obtain RSI-MRI images of high-risk patients before ADT, after ADT but before RT, and after RT.