Part II: "Physics, bitches." The lowdown on MRIs, gadolinium and more
By Howard Wolinsky
Gregory Karczmar, PhD, a medical physicist at the University of Chicago, last week spelled out the mythology of magnetic resonance imaging (MRI) scanner and the need for 1-1.5 Tesla (T) prostate-specific MRI scanners.
Karczmar told me that commonly recommended 3T scanners are popular among radiologists but insisted that less powerful magnets, like 1 to 1.5 T, can do the job.
He said scanner manufacturers are engaged in a magnet arms race—pushing more and powerful and expensive magnets with all the bells and whistles—but really should shift their attention to less powerful prostate-specific MRIs. He envisions such devices will lower costs, enable placement of scanners in easy-access shopping malls, and will change the MRI paradigm by lowering costs and making them available to a broader audience with prostate-specific antigen (PSA) blood levels going down to 2. (See protocol below.)
The medical physicist said they’ll even reduce the incidence of claustrophobia because their tubes, or bores, have a wider diameter.
Karczmar wrote me a follow-up email with some more reasons why prostate-specific MRIs with lower-field magnets ought to be adopted.
Here goes:
—At 3T, we get major magnetic field distortions because of gas and other stuff (as you can imagine, shit speak in plain English). To make things even worse-this stuff moves around so the artifacts change from scan to scan. At lower field (e.g. 1.5 T) these artifacts are much smaller.
—Some critical relaxation times are much longer at lower fields – so we have more time to measure the signal. This gives us nice images and somewhat offsets the loss in signal-to-noise ratio that comes from lower field magnets. (Read the earlier article regarding how the magnets work.)
—We have more flexibility in the kinds of pulse sequences we can use because radio-frequency power deposition is much lower. In addition, the radio frequency pulses that produce the signal work better at lower field and we have more options for designing these pulses operating at a lower frequency.
(Gregory Karczmar, PhD, and his late best friend Madelaine, who died from cancer.)
Egads, gadolinium. Again.
By Howard Wolinsky
I know that gadolinium, the contrast agent, has a source of anxiety for some of you. When we first started support groups for men on active surveillance at AnCan and ASPI, there was a weekly drumbeat of worries about gadolinium.
Men were—and are—worried that gad will cross the blood-brain barrier and cause gadolinium deposition disease (GDD) marked by fatigue and other symptoms. A few physicians and some patients began using the term GDD to describe possible side effects of gadolinium-based contrast agents.
Martial artist and actor Chuck Norris and his wife Gena put GDD on the map when they filed a $10-million suit in state court in San Francisco in November 2017 against several manufacturers of the agents. They alleged that Gena Norris had been poisoned by the contrast agents in several MRIs she underwent to evaluate her arthritis. She blamed GBCAs for "multiple debilitating bouts of pain and burning."
(Chuck Norris as “Walker Texas Ranger” went after gad makers.)
In 2020, the Norrises dropped their lawsuit against Bracco Imaging, a leading gadolinium manufacturer based in Italy. (I don’t know what happened with the other suits.)
(Gena and Chuck Norris)
I wrote about gad in MedPage Today in 2019 in an article entitled “Gadzooks! And Egads! Another Dilemma in Prostate Cancer.” The issue centered mainly around some reports that demonstrated small amounts of gadolinium were detected in autopsies of the brains of patients who died from unrelated causes and who had been given gad contrast for MRI scans.
Men on active surveillance now may undergo a series of MRIs with a potential increased exposure to gad, so naturally many are worried.
(I’ve had two MRIs—both were gad—in the past almost 13 years. So far, so good.)
I had written several articles about how gadolinium really wasn’t a requirement for men with low-risk, small lesions.
But some urologists insisted on gad even though it wasn’t necessary. Urologists may not have known what their radiology colleagues knew. GDD mainly was reported on in the consumer media and less so in the scientific literature.
Several radiologists told me gad was unnecessary for low-risk patients. But felt like a state secret.
The fractured nature of massive medical information was part of the problem. Urologists may have trouble enough keeping up with the research in urology proper without tackling radiology.
Part of the problem is economic. There are extra fees to be had with gad. It’s easy money for radiologists and hospitals.
Radiologists generally don’t speak to patients. They consider themselves the doctor’s doctor. I’ve talked to many patients who want to avoid gad who were blown off by radiologists, who referred them back to their urologists, who were in the dark and just automatically ordered contrast. It was a never-ending cycle.
I asked Gregory Karczmar, the UChicago medical physicist, his perspective on gad.
Karczmar said, “In prostate cancer, gadolinium is not king. In breast cancer, palladium is king. You could imagine doing a prostate screening scan without any injection of contrast and still get a pretty good image."
“According to the PIRADS Committee, contrast-enhanced MRI is the least important part of the study. Our method doesn’t use gadolinium at all. Our method is very good, and you can get a scan without any contrast injection.”
So take that as you will.
Dr. K’s protocol for prostate-specific MRIs
By Howard Wolinsky
Karczmar also has recommendations for a future MRI-focused screening protocol that goes like this:
Genetic testing, PSA, family history, personal history, race, socioeconomics, other clinical tests to determine risk level.
Use a risk model from ‘1’ to determine who needs further screening and how much. From the risk model – build a screening plan for each individual man.
Based on this risk model, you would establish a cutoff to decide who get’s an MRI and what MRI protocol they get.
For example –
high-risk people would probably get a longer contrast-enhanced scan in a hospital setting, and they would be screened with higher frequency. People who are in the lower-risk end of the high-risk category could get a much lower dose of contrast agent.
People with modest risk could receive a very rapid scan without contrast media injection in a community setting, e.g. in a mall, so they don’t have to come into a hospital, and these scans could be less expensive.
Some people would be told that they don’t need screening at all – or maybe they need one MRI scan at age 50 – or something like that.
People at modest risk who have suspicious findings on the community-based MRI screens could be referred to the hospital for more intensive contrast-enhanced screening with MRI.
“All of this would have to be figured out by clinicians and public health experts and would probably change as the technology improves,” said Karczmar.
What about micro-ultrasound, which is starting to compete with MRIs?
Karczmar said, “As ultrasound gets better maybe it could be a substitute for MRI at some points in the process. So in this protocol – different types of MRI protocols – of no MRI at all for some people. So I can’t make a blanket prediction that MRI will become ‘first- line screening’ - there will be different screening protocols for different patients.”
Swedish researchers show benefits of MRI screening
By Howard Wolinsky
The previous story talks about the prospects of protocols for screening for prostate cancer using MRIs (magnetic resonance imaging)--an uncommon topic.
Shuang Hao, MSc, MPH, and colleagues at Karolinska Institutet in Stockholm report Nov. 10 in JAMA Oncology there were benefits to MRI screening. “Compared with PSA screening, MRI-based screening reduced the number of both lifetime biopsies and overdiagnosis by approximately 50%,” they found.
In recent years, there has been growing evidence in favor of MRI combined with targeted biopsies to complement PSA testing and improve prostate cancer diagnostics.
“Screening using the prostate-specific antigen (PSA) test followed by a standard biopsy has been found to reduce prostate cancer mortality However, organized screening remains debatable due to the possibility of unnecessary biopsies with associated adverse effects as well as the high possibility of overdiagnosis and overtreatment of,” researchers said. “Relative to screening with standard biopsies alone, MRI-based screening reduced the number of both lifetime biopsies and overdiagnosis by approximately 50% and had a high probability of being cost-effective than the traditional PSA screening.”
Researchers randomized a total 603 men to the standard arm, 165 of these participants (27.4%) did not undergo standard biopsy; 929 men were randomized to the experimental arm, 111 (11.9%) of whom did undergo MRI or any biopsy. Men were 55 to 69.
“In this economic evaluation study of 1,532 adult men in Sweden, cost-effectiveness analysis showed that MRI-based screening with combined targeted and standard biopsies was associated with reduced lifetime prostate cancer–related deaths and resulted in an incremental cost-effectiveness ratio of US $53,736 per quality-adjusted life-year gained compared with no screening,” Hao said. “Compared with PSA screening, MRI-based screening reduced the number of both lifetime biopsies and overdiagnosis by approximately 50%.”
Researchers concluded results suggest that screening with PSA and MRI with subsequent combined biopsies for prostate cancer has a high probability to be more cost-effective compared with PSA screening using standard biopsy.
Moving AS to the next level
The Active Surveillance Coalition, a collaboration of leading Active Surveillance support groups for patients on AS, sponsored a webinar on Nov. 17 featuring international experts.
Urologists from Holland, the United Kingdom, and the state of Michigan share their “secret sauce” for reaching AS rates of 85-94%.
The program was called “Moving AS to the next level.”
I moderated this meeting and will write it up. But you can view the video now: https://aspatients.org/meeting/moving-as-to-the-next-level-can-we-help-more-patients/
The United States has a lot to learn. It has lagged behind other wealthy countries in AS acceptance though the approach started here and in Canada in the late 1990s.
AS uptake in the U.S. finally reached a majority of 60% in 2021. The American Urological Associationin 2022 set a new goal of 80%.
Come on, that’s still too low as the webinar speakers demonstrated.
In 2010, when I was diagnosed, only 6% of patients qualified for AS opted for this approach. So things are improving.