7 ms·

I did my Masters' thesis with the group that invented and developed this in Toronto. I know some of the co-authors on the paper personally since we worked toget

I did my Masters' thesis with the group that invented and developed this in Toronto. I know some of the co-authors on the paper personally since we worked together. AMA.

radicalbyte 7y ago
Is there any chance that these techniques could be equally effective for other cancers? For example Liver, Kidney, Lung cancers?
- ceejayoz 7y ago
  My understanding is prostate cancer has a particular need for this sort of less invasive approach, as surgical procedures there tend to damage the sensitive equipment nearby - incontinence and impotence are common side effects of it, and often not worth it when prostate cancer tends not to be deadly. Things like liver cancer you're probably better off just doing a surgery for, as you'll have more chance of getting it all, spotting metastasized offshoots, etc., and it's fairly accessible.
- HorizonXP 7y ago
  Yes, very much so. Ultrasound in medicine is very cool technology. Obviously many of us have experience with ultrasound imaging, which has revolutionized medicine in a number of ways. But we also learned that if you crank up the amplitude and frequency, you can heat the tissue. Our research group was one of several that figured out that you can use MRI-based thermometry to measure that heating, and use it as the input to your control loop. Then, it's a matter of adjusting the frequency, amplitude, and positioning (i.e. in this case, rotation) to "paint" your heat pattern. Thus, at least at our site, it was used to develop treatments for uterine fibroids, some types of breast cancer, and some types of brain cancer (using transcranial ultrasound, which is much harder to do because you have to go through bone and adjust for that medium). Generally, areas that you can reach from the skin and/or with a special probe, are potential treatment targets. Lung cancers are hard to treat with ultrasound, for a few reasons. The biggest is that it moves, which makes it hell for the MRI and system as a whole to keep up without hitting unwanted areas. The other is that ultrasound doesn't travel well through air. For ultrasound ablation to work, you need a good conduction interface. That's why ultrasound technicians slather that clear gel on you when they're imaging you. It's possible to do in the lungs, just exceedingly difficult. It's unlikely that someone will commercialize something there. The liver and kidneys won't be targeted either because the only way to reach them is by performing an incision. You might as well use other techniques like laparoscopy.
  - _Microft 7y ago
    Would transcranial ultrasound have the problem of unwanted hotspots because of reflections and a focusing effect of the curvature of the skull? I would assume that this could only be done by scanning the head with a MRI, modelling the tissues in detail, simulating the process and then constructing a wave front from many emitters that does what one wants. Ideally all of that in real time as I guess the heating process will change the properties of the treated tissue in a way that would require it.
    - HorizonXP 7y ago
      Precisely. See Ultrasound attenuation coefficient (https://en.wikipedia.org/wiki/Attenuation#Attenuation_coefficient https://en.wikipedia.org/wiki/Attenuation#Attenuation_coeffi...) You'll note that it's measured in dB/(MHz-cm), and that soft tissue is 0.5, while bone is 6.9. Just like light, anytime ultrasound hits an interface, there are reflections and refractions. Furthermore, since bone attenuates ultrasound so much, you have to increase your amplitude greatly (and even more so with higher frequencies) in order to get enough thermal energy to be deposited at your target. If you don't do it right, you can create dangerous hotspots at the bone-tissue interface, and you can also deposit energy where you didn't intend to. Given that ultrasound therapy intends to be more precise than other techniques, you're kind of defeating the purpose! Edit: in response to your edit, yes that's exactly what they do. They create an array of transmitters to be able to precisely target various locations within the skull. It wasn't my area of research, but I'm pretty sure they used them to create interference patterns as well, so many emitters were activated to work in concert to target one area. See this image: https://sunnybrook.ca/uploads/1/_research/about/fus/3-ultrasoundbraindevice.jpg https://sunnybrook.ca/uploads/1/_research/about/fus/3-ultras...
    - beering 7y ago
      Here's an application of ultrasound towards essential tremors that is already being used on people! https://www.usnews.com/news/health-news/articles/2019-11-20/ultrasound-may-ease-common-form-of-hand-tremor https://www.usnews.com/news/health-news/articles/2019-11-20/... Transcranial ultrasound + monitoring via MRI. Requires a rock-solid transmitter clamped on the skull.
- js2 7y ago
  A similar treatment is available for uterine fibroids (benign smooth muscle tumors, which affect many to most women by age 50): https://www.uclahealth.org/fibroids/mr-guided-focused-ultrasound https://www.uclahealth.org/fibroids/mr-guided-focused-ultras...
Silhouette 7y ago
AMA. Thanks. I'm always wary of reading too much into articles about promising medical developments, because it seems like often the headlines look great but they are actually referring to some relatively early stage of trials, so results of later trials might not be so good or even if they are it might still be a long time before the treatment is used routinely. However, in this case, the article reads as if this is literally a cure for (one sort of) cancer, with an 80% success rate, which can be done as an outpatient procedure with a relatively low risk of complications. That seems like about 80% of the holy grail, at least in terms of treating prostate cancer specifically. Can you give an expert perspective on how excited we should or shouldn't be about this result?
- HorizonXP 7y ago
  I just read the abstract, and I'd say we should be very excited about this result. When I left my Masters in 2012, the clinical trials being done still resulted in a prostatetectomy. Meaning, these generous men donated their time to allow us to use them as guinea pigs, yet received no benefit since their prostates were removed anyway. That did allow us to perform in-depth pathology reports about the efficacy of the treatment. This paper has 115 men that were treated and allowed to not have the surgery done, so this is the first time that we were able to see what the outcomes of the treatment truly are. Based on the results in the abstract, it looks like the hypothesis that men would be "cured" and have a better quality of life (i.e. no incontinence or sexual dysfunction) seems to be well-supported. More of these trials will need to occur before it becomes approved as a viable alternative to surgery. The big benefit though is that even if the the treatment fails to kill all of the cancer, it probably kills enough of it that you can go back to a watchful waiting approach, keep monitoring PSA levels and symptoms, and if anything was missed, follow up with full surgery. That is, surgery can become the last-ditch approach vs. being the only approach.
pstuart 7y ago
Off topic, but if it could shrink the prostrate (to treat BPH) with similar technology that would be awesome. And after a quick search it looks like there's some movement there: https://fusfoundation.org/diseases-and-conditions/urological/benign-prostatic-hyperplasia-bph https://fusfoundation.org/diseases-and-conditions/urological... @HorizonXP, any thoughts on this and it's potential to go mainstream? Asking for a friend...
- always_swapping 7y ago
  It seems that 29 centers in the US do this type of FUS treatment commercially as listed on the FUSF website. Any focused ultrasound tech has potential to gain wide acceptance but it is mostly the imaging component (MRI guided in most cases) that hold it back due to costs and availability.
  - pstuart 7y ago
    Thanks, I skimmed too quickly :-). Time to do further research, you know, for a friend.
    - always_swapping 7y ago
      Best of luck for your friend. I've first hand witnessed FUS in neurological applications and believe it is a game-changer.
    - stevenjohns 7y ago
      Finasteride (and other DHT inhibitors) is an option also worth looking into.
      - pstuart 7y ago
        Yes, but it also has some significant side effects too. Pro: hair growth. Con: decimated libido.
  - 1_over_n 7y ago
Beltiras 7y ago
How much heat are we talking about? General anesthetic amount or local enough?
- HorizonXP 7y ago
  I was about to say definitely general anesthetic, but I'm not 100% sure now. The patients for prostate cancer were definitely put under. I don't know about the uterine fibroid patients though. They might have received an epidural? It's less about the pain of the heat, and more about the discomfort of having probes in your genitals, and the requirement that you stay perfectly still.
- Tharkun 7y ago
  Considering they're putting a rod up your urethra which will be burning you from within, and another device up your rectum, while you're in the uncomfortable confines of an MRI scanner, I suspect local might not be something most people would be comfortable with.
  - thafoobar 7y ago
    Lots wouldn't be comfortable, but there's a few who'd likely be ok with it. Urethral+anal electric stimulation is a relatively known kink. There's no way to keep still in that situation though, so I'd expect anaesthesia would be necessary for that.
Beltiras 7y ago
Is there a plan for following up in 5 years?
- HorizonXP 7y ago
  I think they're following up with these patients yearly. It's the same post-operative care procedure they do with prostatetectomy patients, except they're probably being more thorough here because they have something to prove.
homero 7y ago
Is it like ablation but through skin?
mooreed 7y ago
@HorizonXP first thank you for your willingness to answer questions. 1) Any idea on where to look to find out when this might become available? Looks like it was just cleared by FDA with 510(k) clearance. 2) My guess is that if you want this done - you would have to travel to UCLA? and Dr. Raman (or colleague) would perform the operation? 3) Is there anywhere to find a real discussion of down side risks with actual rates and figures? For example, the RSNA article has a statement: >"There were low rates of severe toxicity and no bowel complications." 4a) What does `severe toxicity` entail? 4b) Is that a operational complication that is remedied at the hospital and overcome in the short-term? or is that a long term quality of life issue? 5a) Furthermore what is this actual "low" rate? is it 2/115 or is more like 10/115? It looks like the base rate for these is perhaps around 3%-7% is how would I compare this study of 115 to something published like: [1] Similarly RSNA states: > "We saw very good results in the patients, with a dramatic reduction of over 90 percent in prostate volume and low rates of impotence with almost no incontinence" --Dr. Raman said. 5b) Where could I look to find the actual rates of each of these negative side effects? 5c) Or would you guess they are not published? [1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900775/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900775/
cperciva 7y ago
The first thing I always think about with ultrasound is how it's used to break up kidney stones. Is there a danger here of breaking up the tumour and thereby allowing cancer cells to spread through the body more easily?
- LinuxBender 7y ago
  I believe it is using heat (from ultrasound oscillation) to burn them. Cells can't survive the heat.
  - cperciva 7y ago
    Yes, I realize that's the intention. My concern is whether ultrasound might unintentionally break up the tumour and release cancerous cells to spread throughout the body.
    - LinuxBender 7y ago
      I am not a doctor nor an expert in this area, but I would presume that would be a valid risk if the frequency were not tuned specifically to resonate the tumor prior to increasing the amplitude. And then there is the matter of focus / accuracy. Perhaps nih.gov has a study with numbers to show the attainable accuracy and what statistics are given back to the equipment and the doctor to compensate and tune the signal. My understanding is that the inverse is generally true, in that, there is too much heat and the surrounding area is scarred.
dmix 7y ago
How long does the whole procedure take?

I did my Masters' thesis with the group that invented and developed this in Toronto. I know some of the co-authors on the paper personally since we worked together. AMA.

radicalbyte 7y ago

Is there any chance that these techniques could be equally effective for other cancers? For example Liver, Kidney, Lung cancers?

ceejayoz 7y ago
My understanding is prostate cancer has a particular need for this sort of less invasive approach, as surgical procedures there tend to damage the sensitive equipment nearby - incontinence and impotence are common side effects of it, and often not worth it when prostate cancer tends not to be deadly. Things like liver cancer you're probably better off just doing a surgery for, as you'll have more chance of getting it all, spotting metastasized offshoots, etc., and it's fairly accessible.
HorizonXP 7y ago
Yes, very much so. Ultrasound in medicine is very cool technology. Obviously many of us have experience with ultrasound imaging, which has revolutionized medicine in a number of ways. But we also learned that if you crank up the amplitude and frequency, you can heat the tissue. Our research group was one of several that figured out that you can use MRI-based thermometry to measure that heating, and use it as the input to your control loop. Then, it's a matter of adjusting the frequency, amplitude, and positioning (i.e. in this case, rotation) to "paint" your heat pattern. Thus, at least at our site, it was used to develop treatments for uterine fibroids, some types of breast cancer, and some types of brain cancer (using transcranial ultrasound, which is much harder to do because you have to go through bone and adjust for that medium). Generally, areas that you can reach from the skin and/or with a special probe, are potential treatment targets. Lung cancers are hard to treat with ultrasound, for a few reasons. The biggest is that it moves, which makes it hell for the MRI and system as a whole to keep up without hitting unwanted areas. The other is that ultrasound doesn't travel well through air. For ultrasound ablation to work, you need a good conduction interface. That's why ultrasound technicians slather that clear gel on you when they're imaging you. It's possible to do in the lungs, just exceedingly difficult. It's unlikely that someone will commercialize something there. The liver and kidneys won't be targeted either because the only way to reach them is by performing an incision. You might as well use other techniques like laparoscopy.
- _Microft 7y ago
  Would transcranial ultrasound have the problem of unwanted hotspots because of reflections and a focusing effect of the curvature of the skull? I would assume that this could only be done by scanning the head with a MRI, modelling the tissues in detail, simulating the process and then constructing a wave front from many emitters that does what one wants. Ideally all of that in real time as I guess the heating process will change the properties of the treated tissue in a way that would require it.
  - HorizonXP 7y ago
    Precisely. See Ultrasound attenuation coefficient (https://en.wikipedia.org/wiki/Attenuation#Attenuation_coefficient https://en.wikipedia.org/wiki/Attenuation#Attenuation_coeffi...) You'll note that it's measured in dB/(MHz-cm), and that soft tissue is 0.5, while bone is 6.9. Just like light, anytime ultrasound hits an interface, there are reflections and refractions. Furthermore, since bone attenuates ultrasound so much, you have to increase your amplitude greatly (and even more so with higher frequencies) in order to get enough thermal energy to be deposited at your target. If you don't do it right, you can create dangerous hotspots at the bone-tissue interface, and you can also deposit energy where you didn't intend to. Given that ultrasound therapy intends to be more precise than other techniques, you're kind of defeating the purpose! Edit: in response to your edit, yes that's exactly what they do. They create an array of transmitters to be able to precisely target various locations within the skull. It wasn't my area of research, but I'm pretty sure they used them to create interference patterns as well, so many emitters were activated to work in concert to target one area. See this image: https://sunnybrook.ca/uploads/1/_research/about/fus/3-ultrasoundbraindevice.jpg https://sunnybrook.ca/uploads/1/_research/about/fus/3-ultras...
  - beering 7y ago
    Here's an application of ultrasound towards essential tremors that is already being used on people! https://www.usnews.com/news/health-news/articles/2019-11-20/ultrasound-may-ease-common-form-of-hand-tremor https://www.usnews.com/news/health-news/articles/2019-11-20/... Transcranial ultrasound + monitoring via MRI. Requires a rock-solid transmitter clamped on the skull.
js2 7y ago
A similar treatment is available for uterine fibroids (benign smooth muscle tumors, which affect many to most women by age 50): https://www.uclahealth.org/fibroids/mr-guided-focused-ultrasound https://www.uclahealth.org/fibroids/mr-guided-focused-ultras...

Silhouette 7y ago

AMA. Thanks. I'm always wary of reading too much into articles about promising medical developments, because it seems like often the headlines look great but they are actually referring to some relatively early stage of trials, so results of later trials might not be so good or even if they are it might still be a long time before the treatment is used routinely. However, in this case, the article reads as if this is literally a cure for (one sort of) cancer, with an 80% success rate, which can be done as an outpatient procedure with a relatively low risk of complications. That seems like about 80% of the holy grail, at least in terms of treating prostate cancer specifically. Can you give an expert perspective on how excited we should or shouldn't be about this result?

HorizonXP 7y ago
I just read the abstract, and I'd say we should be very excited about this result. When I left my Masters in 2012, the clinical trials being done still resulted in a prostatetectomy. Meaning, these generous men donated their time to allow us to use them as guinea pigs, yet received no benefit since their prostates were removed anyway. That did allow us to perform in-depth pathology reports about the efficacy of the treatment. This paper has 115 men that were treated and allowed to not have the surgery done, so this is the first time that we were able to see what the outcomes of the treatment truly are. Based on the results in the abstract, it looks like the hypothesis that men would be "cured" and have a better quality of life (i.e. no incontinence or sexual dysfunction) seems to be well-supported. More of these trials will need to occur before it becomes approved as a viable alternative to surgery. The big benefit though is that even if the the treatment fails to kill all of the cancer, it probably kills enough of it that you can go back to a watchful waiting approach, keep monitoring PSA levels and symptoms, and if anything was missed, follow up with full surgery. That is, surgery can become the last-ditch approach vs. being the only approach.

pstuart 7y ago

Off topic, but if it could shrink the prostrate (to treat BPH) with similar technology that would be awesome. And after a quick search it looks like there's some movement there: https://fusfoundation.org/diseases-and-conditions/urological/benign-prostatic-hyperplasia-bph https://fusfoundation.org/diseases-and-conditions/urological... @HorizonXP, any thoughts on this and it's potential to go mainstream? Asking for a friend...

always_swapping 7y ago
It seems that 29 centers in the US do this type of FUS treatment commercially as listed on the FUSF website. Any focused ultrasound tech has potential to gain wide acceptance but it is mostly the imaging component (MRI guided in most cases) that hold it back due to costs and availability.
- pstuart 7y ago
  Thanks, I skimmed too quickly :-). Time to do further research, you know, for a friend.
  - always_swapping 7y ago
    Best of luck for your friend. I've first hand witnessed FUS in neurological applications and believe it is a game-changer.
  - stevenjohns 7y ago
    Finasteride (and other DHT inhibitors) is an option also worth looking into.
    - pstuart 7y ago
      Yes, but it also has some significant side effects too. Pro: hair growth. Con: decimated libido.
- 1_over_n 7y ago

Beltiras 7y ago

How much heat are we talking about? General anesthetic amount or local enough?

HorizonXP 7y ago
I was about to say definitely general anesthetic, but I'm not 100% sure now. The patients for prostate cancer were definitely put under. I don't know about the uterine fibroid patients though. They might have received an epidural? It's less about the pain of the heat, and more about the discomfort of having probes in your genitals, and the requirement that you stay perfectly still.
Tharkun 7y ago
Considering they're putting a rod up your urethra which will be burning you from within, and another device up your rectum, while you're in the uncomfortable confines of an MRI scanner, I suspect local might not be something most people would be comfortable with.
- thafoobar 7y ago
  Lots wouldn't be comfortable, but there's a few who'd likely be ok with it. Urethral+anal electric stimulation is a relatively known kink. There's no way to keep still in that situation though, so I'd expect anaesthesia would be necessary for that.

Beltiras 7y ago

Is there a plan for following up in 5 years?

HorizonXP 7y ago
I think they're following up with these patients yearly. It's the same post-operative care procedure they do with prostatetectomy patients, except they're probably being more thorough here because they have something to prove.

homero 7y ago

Is it like ablation but through skin?

mooreed 7y ago

@HorizonXP first thank you for your willingness to answer questions. 1) Any idea on where to look to find out when this might become available? Looks like it was just cleared by FDA with 510(k) clearance. 2) My guess is that if you want this done - you would have to travel to UCLA? and Dr. Raman (or colleague) would perform the operation? 3) Is there anywhere to find a real discussion of down side risks with actual rates and figures? For example, the RSNA article has a statement: >"There were low rates of severe toxicity and no bowel complications." 4a) What does `severe toxicity` entail? 4b) Is that a operational complication that is remedied at the hospital and overcome in the short-term? or is that a long term quality of life issue? 5a) Furthermore what is this actual "low" rate? is it 2/115 or is more like 10/115? It looks like the base rate for these is perhaps around 3%-7% is how would I compare this study of 115 to something published like: [1] Similarly RSNA states: > "We saw very good results in the patients, with a dramatic reduction of over 90 percent in prostate volume and low rates of impotence with almost no incontinence" --Dr. Raman said. 5b) Where could I look to find the actual rates of each of these negative side effects? 5c) Or would you guess they are not published? [1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900775/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900775/

cperciva 7y ago

The first thing I always think about with ultrasound is how it's used to break up kidney stones. Is there a danger here of breaking up the tumour and thereby allowing cancer cells to spread through the body more easily?

LinuxBender 7y ago
I believe it is using heat (from ultrasound oscillation) to burn them. Cells can't survive the heat.
- cperciva 7y ago
  Yes, I realize that's the intention. My concern is whether ultrasound might unintentionally break up the tumour and release cancerous cells to spread throughout the body.
  - LinuxBender 7y ago
    I am not a doctor nor an expert in this area, but I would presume that would be a valid risk if the frequency were not tuned specifically to resonate the tumor prior to increasing the amplitude. And then there is the matter of focus / accuracy. Perhaps nih.gov has a study with numbers to show the attainable accuracy and what statistics are given back to the equipment and the doctor to compensate and tune the signal. My understanding is that the inverse is generally true, in that, there is too much heat and the surrounding area is scarred.

dmix 7y ago

How long does the whole procedure take?