STFC-RAL-CR03 R61: And let us introduce, our speaker, Ken Long, today. Just, well, a few short bio, which I found interesting.
STFC-RAL-CR03 R61: So we can, lease the development at Lara will hear today from Imperial, and as part of PPD.
STFC-RAL-CR03 R61: LARA activities are supported by the Center for Clinical Application of Particles, also called CCAP.
STFC-RAL-CR03 R61: which Ken is the director.
STFC-RAL-CR03 R61: This is a multidisciplinary collaboration of personnel from various research fields and groups.
STFC-RAL-CR03 R61: His research interests also include the development of the MEON accelerator to serve the future high-precision neutrino experiments, and as the
STFC-RAL-CR03 R61: basis for a multi-TV immune collider. So he was a spokesperson of the mice.
STFC-RAL-CR03 R61: Experiment.
STFC-RAL-CR03 R61: Muon ionization query experiment.
STFC-RAL-CR03 R61: And these activities originated in the publication in the nature of the demonstration of ionization coding.
STFC-RAL-CR03 R61: So, what it felt, I copied that.
STFC-RAL-CR03 R61: all these activities is also based on this fixed field of the methane-ready accelerator technology, which is essential both for LARA and the mute one.
STFC-RAL-CR03 R61: So, over to you. Thank you.
STFC-RAL-CR03 R61: 28 is reducing number of times, I'll presume.
STFC-RAL-CR03 R61: see if that's different in the example. Great advice.
STFC-RAL-CR03 R61: 100 years ago, I would have tried to update, you know. So,
STFC-RAL-CR03 R61: This is a very different project,
STFC-RAL-CR03 R61: And I hope by the end of it, you're going to be really enthused and think that it's a good thing.
STFC-RAL-CR03 R61: So let's start with, the grand motivation. Everybody knows that cancer is a big challenge.
STFC-RAL-CR03 R61: How are the people
STFC-RAL-CR03 R61: will get cancer during their… their lifetimes. It's the most common cause of death across the world. Well, the second most common cause of death across the world. The first is currently hot seed, I think. There's a significant
STFC-RAL-CR03 R61: Growth in demand,
STFC-RAL-CR03 R61: projected. If you look at the, let's say, the high-income countries, where the record was not, there's a doubling predictive between now and 20135.
STFC-RAL-CR03 R61: That doesn't take into account all the places where the statistics are not being kept, so the low- and middle-income countries, where there's enormous unmet needs. So in order to meet that projected unmet need, and the, sort of, estimated unmet need, you really need new techniques which can be rolled out more broadly.
STFC-RAL-CR03 R61: The most motivating thing to me, if you look at the radiation therapy, which is, which is used in 50% of cancer treatments.
STFC-RAL-CR03 R61: is implicated in 40% of cancer cures.
STFC-RAL-CR03 R61: Today, the, the systems…
STFC-RAL-CR03 R61: The X-ray systems are relatively compact, but the particle beam systems are enormous. That really comes down to the beam delivery system.
STFC-RAL-CR03 R61: But the patient restraint in order to keep the patient still, stop performance, moving.
STFC-RAL-CR03 R61: and to be able to reproduce the position between treatments, they are quite, I find them quite scary, so I pick out a scary
STFC-RAL-CR03 R61: versioning of a head restraint for a patient, and honestly, if you think about the triggering activity at LHC, the decisions you make in a microsecond, if you could roll those out into radiotherapy, there's nothing in the human body that moves very far in a microsecond.
STFC-RAL-CR03 R61: So there's… there's really an opportunity to harness novel techniques for clinical benefit.
STFC-RAL-CR03 R61: And, sort of, as a…
STFC-RAL-CR03 R61: I just want to say this now, in the sense of how do you develop particle physics, let's say, beyond FCC, we really need new acceleration techniques in order to take the energy frontier.
STFC-RAL-CR03 R61: further, and maybe this is one. Right, so why particles instead of photons?
STFC-RAL-CR03 R61: at some point in such talk, everybody has a slide like this. So the right-hand side is a… is a treatment of a spinal tumor.
STFC-RAL-CR03 R61: done with x-rays. The beams are shot in from the back, And,
STFC-RAL-CR03 R61: You can see that the dose is concentrated.
STFC-RAL-CR03 R61: Around the spinal cord, but there's a lot of dose being delivered into the organs in the thorax.
STFC-RAL-CR03 R61: So this is causing damage, it's a pediatric treatment, so the person has a long time to live for secondary tumors to develop. If you deliver that using protons, because of the Bragg peak, so the way that the protons are losing energy, you can confine the dose into the region you want. So there's a big advantage that's coming from the way that energy is lost.
STFC-RAL-CR03 R61: And,
STFC-RAL-CR03 R61: Well, I'm teaching you suck eggs, everybody knows this, it's in the Particle Data Book, but the Particle Data book is plotted this way around, if you…
STFC-RAL-CR03 R61: If you look at it.
STFC-RAL-CR03 R61: So if you shoot protons in, they lose energy by ionizing the material. As they slow down, the energy transfer becomes more and more efficient, until there's a place where they're not moving very fast at all, and they lose all of the energy in a very rapid manner, and so you get a very sharp peak in the energy spectrum.
STFC-RAL-CR03 R61: So this is, the proton beam with a bright peak here. X-rays, the dose, develops as the shower is developing, then there's a place where there's essentially an exponential decay.
STFC-RAL-CR03 R61: And you're delivering energy to the tissues, for a significant distance, even further ado patients.
STFC-RAL-CR03 R61: If you look at heavier lines, so here's the lines of carbon, you can see that the energy decomposition is more peaked.
STFC-RAL-CR03 R61: But there's a tail. The tail is coming from nuclear fragments, so your, big advantage of proton beam is you can stop the dose
STFC-RAL-CR03 R61: By calculating the wave, for heavier arms, there is a complication.
STFC-RAL-CR03 R61: That you get leakage, beyond the… beyond the bracket.
STFC-RAL-CR03 R61: Okay.
STFC-RAL-CR03 R61: If you want to make something in the therapeutic, you want to go live, so I'm a sort of…
STFC-RAL-CR03 R61: A graph without axis, which is…
STFC-RAL-CR03 R61: Not very good. So, if you look at the response probability, so you either have tumor control, or you have normal tissue complications, so this is, descriptive. These are the probabilities of either good effects or bad effects as a function of dose. What you want to do is to separate
STFC-RAL-CR03 R61: We want to be able to give as much dose as possible.
STFC-RAL-CR03 R61: To control the tumor, while having,
STFC-RAL-CR03 R61: Having as little negative effects on healthy tissue, and that gap is called the urgent.
STFC-RAL-CR03 R61: X-ray therapy, as you know, is widely used. It's the most widely used Technically radiotherapy.
STFC-RAL-CR03 R61: Those scores exponentially with death terms of What do you indicate.
STFC-RAL-CR03 R61: And that means that the dosant's often limited by the proximity of sensitive all.
STFC-RAL-CR03 R61: So there's a real advantage if you can use programs.
STFC-RAL-CR03 R61: I'll put you back quickly.
STFC-RAL-CR03 R61: So…
STFC-RAL-CR03 R61: Little across the world, you want to have a wide, broad access to particle bead therapy. You look, in the relevant websites, you can find that there are 70 plus, the number keeps going up slowly, so call it between 70 and 100 particle bead therapy centers in operation.
STFC-RAL-CR03 R61: Probably the sum is probably something we're just concerned. So, several… well, many are under construction.
STFC-RAL-CR03 R61: These, are being developed. There's an incremental development of technique which is being done by, the existing medical equipment suppliers, and of course, research, universities and in labs.
STFC-RAL-CR03 R61: There are also new initiatives, so Solana is one, but there are, of course, others across the world.
STFC-RAL-CR03 R61: I draw your attention to the map, so you can find this on the web.
STFC-RAL-CR03 R61: I mean, reasonably enough, the, the programmed therapy centers are concentrated in, places where there's a lot of New York's. So that'd be North America, Europe.
STFC-RAL-CR03 R61: I'm in Asia.
STFC-RAL-CR03 R61: Okay.
STFC-RAL-CR03 R61: So,
STFC-RAL-CR03 R61: I'm gonna… well, let me just move on. There's some exciting indications that if you deliver the beams in non-standard ways, you can have clinical benefit.
STFC-RAL-CR03 R61: I wanted to… Just mention size, because size is important.
STFC-RAL-CR03 R61: In the UK,
STFC-RAL-CR03 R61: Today, there are two particle beam particles tend to be run by the NHS, which are based on cyclotron. Cyclotron-based facilities have, sort of technical limitations in that you can't modulate the energy of the beam which emerges from the cyclotron, so people put material in the way to slow it down, that degrades the beam.
STFC-RAL-CR03 R61: And the instantaneous dose rate is limited at extraction, and
STFC-RAL-CR03 R61: Well, the current is very large, actually, if you have the right kind of psychotron, but the instantaneous dose rate is relatively low, and therefore, in order to deliver high dose rates, which are indicated.
STFC-RAL-CR03 R61: as I'll try and explain, and it's going to be comfortable.
STFC-RAL-CR03 R61: If you look at the size of the building, the cycle is sitting here, so the size of the accelerator really is not the driving term. The way that the beam is delivered to the patient, you want to shoot the beam from all directions in order that you can localize the dose in the tumour and limit the amount of entry dose
STFC-RAL-CR03 R61: And the dose to healthy tissue.
STFC-RAL-CR03 R61: So what that means is that the beam delivery system, has a transport, but then it goes through what's called a gantry, so this
STFC-RAL-CR03 R61: It's something which raises the beam, turns it through 90 degrees, and shoots it back into the patient. That's an engineering tour de force. The gantry system weighs more than 400 tons.
STFC-RAL-CR03 R61: Depends exactly how it's done. For irons, it can be even heavier. If you say you're on floor 1 of a building, your treatment
STFC-RAL-CR03 R61: room is on the first floor. Then the gantry will be such that you take drawers to and
STFC-RAL-CR03 R61: the ground floor into account as it rotates. Engineering toward a force in the sense that that 400-ton object rotates around a fulcrum, which is accurate up to less than a millimeter.
STFC-RAL-CR03 R61: But it's large and complicated, and you can have two national centres in a country like the UK.
STFC-RAL-CR03 R61: So this is, this is a crispy in Manchester UCL agent.
STFC-RAL-CR03 R61: London, to…
STFC-RAL-CR03 R61: The other way of doing it is to use a synchrotron. Synchrotron is a little bit bigger than the cyclotron.
STFC-RAL-CR03 R61: But, of course, you know, so this is, smaller than ISIS, but it's that kind of scale. You've still got the gantries. The advantage of the cyclotron is that, you can make ions effectively, and accelerate them to high energy. Now, of course, you have an enormous gantry, because in the beginning, you become the
STFC-RAL-CR03 R61: I'm sorry, Bob.
STFC-RAL-CR03 R61: If you put Lara on that scale, so I admit I'm cheating a little bit.
STFC-RAL-CR03 R61: Then, this part of the main Austrong facility in Wienstadt was, yeah, no.
STFC-RAL-CR03 R61: is… is scales like this. Obviously, we're not treating patients. This goes up to several hundred MeV. Our baseline proton energy is 127 MeV, but I'm making the point about size. Size equates to an investment cost
STFC-RAL-CR03 R61: So, we're reducing the size and their public costs.
STFC-RAL-CR03 R61: A complexity of the facility.
STFC-RAL-CR03 R61: I think the other part that we want to be able to do with the laser driven approach is we want to increase the flexibility, so different iron species, different kind of bean profiles, I'll try and motivate those in a minute, in order that one can optimize
STFC-RAL-CR03 R61: The treatments, eventually.
STFC-RAL-CR03 R61: It's not all about the accelerator. So, it's a pretty picture, but it's supposed to allow me to say two things.
STFC-RAL-CR03 R61: If you reduce the size, that reduces the investment cost.
STFC-RAL-CR03 R61: If you increase throughput, in principle, you can reduce the cost of treatment, so long as the indications
STFC-RAL-CR03 R61: clinically are there. So we want to increase the automation, we want to monitor the motion, so both of the patient tissues, and
STFC-RAL-CR03 R61: And then, in the LXC triggering sense, we want to be able to shoot the beam when the stars are aligned, and that way we can remove the need for the gantry.
STFC-RAL-CR03 R61: And perhaps moves A little bit, a 70 kilogram object, which is the human.
STFC-RAL-CR03 R61: Rather than the 400-ton object, which is the camera.
STFC-RAL-CR03 R61: Okay, and that, in principle, would reduce the cost of treatment.
STFC-RAL-CR03 R61: So I wanted to do a historical interlude, because I think there's a message for it which is important. So, probably most people here have gone to the Fermilab, and there's Robert Ruth from Wilson Hall.
STFC-RAL-CR03 R61: She's the high-rise there.
STFC-RAL-CR03 R61: Robert Wilson worked on the Manhammen project, and he came out of the war wanting to do something good with radiation.
STFC-RAL-CR03 R61: And he wrote a paper about how you could beat cancer with, beams, so X-ray beams were already being used.
STFC-RAL-CR03 R61: And maybe just look at this figure from the paper that he wrote in 1946. He's got a proton beam B with the Bragg peak. He notes that, the, a single proton would be narrower than the beam of protons. He also points out the carbon would be more narrow.
STFC-RAL-CR03 R61: electrons would be more broad. So he's got the whole basis of the modern, technique there, and they did develop a cyclotron, which was eventually,
STFC-RAL-CR03 R61: He's all the clerk.
STFC-RAL-CR03 R61: The other thing I wanted to point out was, like, this is a Livingston plot, of course, but the history
STFC-RAL-CR03 R61: of the accelerated development and, and the use. The Cytotron was invented, as everybody knows, by Lawrence around 1932.
STFC-RAL-CR03 R61: Secretron in 1946, If you look at the exploitation of that medicine or biology.
STFC-RAL-CR03 R61: The first biological studies were done with cyclotrons in 48, so that's relatively quick, but it's, 16 years.
STFC-RAL-CR03 R61: Preclinical studies,
STFC-RAL-CR03 R61: of the radiation of the pituitary gland had to wait until 1954. The first treatment for cancer is 1974.
STFC-RAL-CR03 R61: So, in 1974, there was the SPS at CERN.
STFC-RAL-CR03 R61: So it's not about the accelerator technique. This long gap is about how you control the beam, how you know the beam that you shoot into the patient.
STFC-RAL-CR03 R61: The instrumentation, and so it's the system aspects that have taken the long time. And, okay, so we mustn't make that mistake a second time with the laser-driven approach.
STFC-RAL-CR03 R61: So, in order to have an initiative where we're going to use normal techniques to enhance
STFC-RAL-CR03 R61: Biomedical research and, eventually clinical
STFC-RAL-CR03 R61: activities. We need to be looking at the source, so the accelerator part, the source to capture.
STFC-RAL-CR03 R61: and the novel acceleration in order to preserve the beam structure. We absolutely need to be masters of novel…
STFC-RAL-CR03 R61: Real-time dosimetry instrumentation, image processing, and importantly, feedback to the beam.
STFC-RAL-CR03 R61: Because…
STFC-RAL-CR03 R61: Because, just like, on the battlefield, if you're an artillery captain, you shoot the shell, see where it goes, and then you adjust,
STFC-RAL-CR03 R61: In order that you don't overshoot or undershoot.
STFC-RAL-CR03 R61: I'm going to show you some data from what is known about radiation in tissue, and there's a lot of fundamental radiation biology that needs to be done in order to improve the treatment plan.
STFC-RAL-CR03 R61: So that, if you like, is the initiative that we're trying to execute, and I'll try and show you how far we've got.
STFC-RAL-CR03 R61: So we formed an ARA collaboration.
STFC-RAL-CR03 R61: In the, funding last day… context, LARA was developed in the… in… through the infrastructure fund.
STFC-RAL-CR03 R61: To serve the Island Therapy Research Facility,
STFC-RAL-CR03 R61: And that's allowed us to make CVR. It's a lot of the things I'm going to talk about copying CVR. The mission of the collaboration
STFC-RAL-CR03 R61: After a lot of discussion, is that we want to deliver a systematic and definitive radiation biology program using the techniques that we want to develop, or we think can be developed for clinical
STFC-RAL-CR03 R61: I mean… political practice.
STFC-RAL-CR03 R61: By doing this, all day, every day, doing science, we want to prove the feasibility of the laser-driven hybrid acceleration approach.
STFC-RAL-CR03 R61: And that way, we'll lay the foundation for a transformation of what you're doing therapy.
STFC-RAL-CR03 R61: I think, the LARA collaboration, in particular with SDFC, is the… is the bedrock, if you like, on which we can build, that, activity.
STFC-RAL-CR03 R61: Right.
STFC-RAL-CR03 R61: So we're gonna do some science, but, but, perhaps not terribly familiar science.
STFC-RAL-CR03 R61: First of all, I want to show you the data which is used in the treatment planning software, so that if you would
STFC-RAL-CR03 R61: go to receive such treatment. This is kind of the kind of data that is used.
STFC-RAL-CR03 R61: So, if you look at the graph on the vertical axis, you've got relative biological effectiveness.
STFC-RAL-CR03 R61: So what that is, is the, is, if you look at… a particular…
STFC-RAL-CR03 R61: A desired endpoint, like killing 50% of cancer cells or something else.
STFC-RAL-CR03 R61: This is the ratio of the
STFC-RAL-CR03 R61: The biological effectiveness that you get with a reference radiation, so, for example, strontium-90,
STFC-RAL-CR03 R61: So the photons from the light are the reference. Do they…
STFC-RAL-CR03 R61: Reference… so it's the radiation that you give. So, for example, the proton radiation.
STFC-RAL-CR03 R61: So for a particular dose, you look at the outcome of your endpoint, so cell… fracture of cell death.
STFC-RAL-CR03 R61: And you've got it on the graph. The different points are different measurements, in vitro and in vivo.
STFC-RAL-CR03 R61: The value that's used in the treatment planning software is 1.1, and I invite you to look at the way that 1.1 does describe the data, but look at the spread, and look at the variation between the measurements.
STFC-RAL-CR03 R61: And in a way, you'd love to do better.
STFC-RAL-CR03 R61: From a natural scientist's point of view, It's also…
STFC-RAL-CR03 R61: important to note that this RBE has an intrinsic variation, like you see there, but it depends on the energy, the iron species, the dose, the rate at which the dose is delivered, the tissue type, and the endpoint that you're considering. So, if you like, there's a huge number of things that you need to control in order to
STFC-RAL-CR03 R61: get the right RV for your treatment.
STFC-RAL-CR03 R61: If you look at, heavier ions, so here there's a compilation
STFC-RAL-CR03 R61: The vines from proton to carbon, neon, and heavier on.
STFC-RAL-CR03 R61: What you see on the… on the vertical axis is their antibiological effectiveness, and the horizontal axis is linear energy transfer, that's DEDX.
STFC-RAL-CR03 R61: In our job. And I just invite you to look at the spread.
STFC-RAL-CR03 R61: The heavier ions are less well known, simply because there are fewer places where the experiments are being done.
STFC-RAL-CR03 R61: So, again, systematic approach would be very important.
STFC-RAL-CR03 R61: normal beep.
STFC-RAL-CR03 R61: So, typically, one gives, the radiation dose is given in a uniform way that covers the tumor. Typically, it's given at several gray per minute.
STFC-RAL-CR03 R61: People have looked or studied
STFC-RAL-CR03 R61: different ways of delivering the radiation. So instead of having a field which is uniform, you can split it up spatially. The important thing seems to be that the… that in the gap, the radiation goes to zero. So you have, say, a millimeter wide.
STFC-RAL-CR03 R61: a millimeter or so gap, but the dose has to go to zero in the gap. So this is spatially fractionated radiotherapy. Natural radiotherapy means you deliver the dose much, much faster. So instead of a few grey per minute, you're delivering 40 grain per second, so it's like 200 times
STFC-RAL-CR03 R61: And in both of those cases, what people have found is the same tumor kill probability, but much
STFC-RAL-CR03 R61: Less, normal tissue damage.
STFC-RAL-CR03 R61: Okay, and that would mean that you could increase the dose.
STFC-RAL-CR03 R61: So, I don't really want to go through the details, but if you look at Flash,
STFC-RAL-CR03 R61: So, delivering the dose very rapidly.
STFC-RAL-CR03 R61: If you look at the different, images of cells.
STFC-RAL-CR03 R61: cultures which have been irradiated, you can see that the damage lesions are much less for the more rapidly delivered, radiation. My point in putting this slide up is to look at the timeline.
STFC-RAL-CR03 R61: The effect, the flash effect, was really invigorated in 2014.
STFC-RAL-CR03 R61: after studies in different, kind of, small animal-based models, it was 5 years until there were, there was treatment. So, to really, by studying the radiation biology, one can make difference, quite rapidly.
STFC-RAL-CR03 R61: So Josie McGarry, well, she just graduated from Imperium, now a postdoc, so she made a study of all the data which exists on proton flash.
STFC-RAL-CR03 R61: In order to try and establish the correlations and to see what was important. So she studied things such as the mean dose rate.
STFC-RAL-CR03 R61: And to look at different ways of quantifying the, benefit.
STFC-RAL-CR03 R61: or the lack of normal tissue, damage. So,
STFC-RAL-CR03 R61: So what you're seeing here is, she has a normal tissue sparing score, which, please read her thesis or her paper to find out what it means, as a function of the mean dose rate. You can plot that and find the correlation. You can indeed find that there is a, positive correlation with the dose rate.
STFC-RAL-CR03 R61: And then you can do some statistics on that. But I think that, we would also think that a horizontal line describes that data quite well.
STFC-RAL-CR03 R61: If you look at all the beam kind of parameters, and a variety of metrics by which you could look for, benefit from the flash effect.
STFC-RAL-CR03 R61: The darker red is a stronger correlation, either positive or negative, and then there's a lot of statistics that you did to look at this. But I think my point here is that, it's not compelling when you look at the data as a whole. There has been benefits. I'm not saying that the treatment should not be
STFC-RAL-CR03 R61: done. I'm saying that the systematic study is very important to find out
STFC-RAL-CR03 R61: Where the effect is, most… Most… exist most, and…
STFC-RAL-CR03 R61: How… and to try and understand it so that you can predict
STFC-RAL-CR03 R61: How it should be used.
STFC-RAL-CR03 R61: Okay.
STFC-RAL-CR03 R61: So a similar, set of arguments for me, especially vaccinated radiotherapy. For a brain tumor irradiation, just to set the scale, this is, a normal uniform irradiation, and here are the beamlets that I'm trying to describe a little while ago.
STFC-RAL-CR03 R61: There's the same evidence of, mortgages varying.
STFC-RAL-CR03 R61: Josie did the same kind of study, so here, this is the dose in the valley. It seems to be very important that the dose is extinguished in the valley.
STFC-RAL-CR03 R61: This is the increased lifespan of small animal models that were irradiated, and here's the same kind of picture. So once again, I think you can see that there is indications in the data, but the data needs to be significantly improved in order to make that.
STFC-RAL-CR03 R61: Sorry, to understand the fact.
STFC-RAL-CR03 R61: Okay, so, so… If you are designing the ideal facility in order to study in science.
STFC-RAL-CR03 R61: What you would love to have is something where you can vary the beam parameters in the time domain, so you want to be able to have short passes, long passes, span the gap between conventional
STFC-RAL-CR03 R61: delivery of low dose rate, very high dose rate. If you want to be able to make mini beans and microbeads, you want to be able to do those at high…
STFC-RAL-CR03 R61: blocks, so, broken up. You want to vary the iron species because, because… because the energy deposition changes with the iron species. You obviously want to change the energy.
STFC-RAL-CR03 R61: And you want to do all of that in combination with other ways of treating cancer, for example, the chemotherapies and the immunotherapy. In fact, there's evidence that giving radiation therapy enhances the effect of the immunotherapy, okay? So, ideally, you would create a system which does all of that.
STFC-RAL-CR03 R61: I want to point out one thing, that, if you… well, this comes from the web, but you can look at the diff… the timescale in which different things happen.
STFC-RAL-CR03 R61: The interaction with the tissues of the beam is over before it starts, that sort of thing. So this happens in 10 to the minus some large number of seconds. Then there's a chemical phase and the biological phase.
STFC-RAL-CR03 R61: People are able to look at the evolution of the biological phase, because after minutes or hours, one is able to study how the effect of radiation evolved.
STFC-RAL-CR03 R61: Nobody has made a beam at the moment which allows you to look at the sub-second evolution of the biological effect. So I think the time domain is a key performance indicator for LARA. We want to be able to exploit the triggerability of the laser source
STFC-RAL-CR03 R61: Just let you do it.
STFC-RAL-CR03 R61: Time Evolution of the Biology Group.
STFC-RAL-CR03 R61: If we want to do all of these things together, we need to have a multidisciplinary collaboration.
STFC-RAL-CR03 R61: There are many initiatives like ours around the world that we've…
STFC-RAL-CR03 R61: Let's call it half a dozen.
STFC-RAL-CR03 R61: The way we have distinguished ourselves is we've really tried to forge the collaboration, which is what it has been in the beginning.
STFC-RAL-CR03 R61: I think that's a… that's a key difference.
STFC-RAL-CR03 R61: Right, so that was all the introduction. Now I'll try and tell you about the project itself.
STFC-RAL-CR03 R61: It's always a lot, right?
STFC-RAL-CR03 R61: Well, we want to have… NARA stands for Laser Hybrid Accelerator for Radiobiological Applications.
STFC-RAL-CR03 R61: It's a normal hybrid approach.
STFC-RAL-CR03 R61: The laser accelerator enthusiasts want to get the high energy with the laser. We want to pick off the flux where it's large, and, stabilize it, and then use
STFC-RAL-CR03 R61: Tightly build state-of-the-art acceleration to give the energy for the treatment.
STFC-RAL-CR03 R61: Okay, so you want to take a laser-driven proton and iron source,
STFC-RAL-CR03 R61: That will allow us to overcome the instantaneous dose rate limitation, which happens at the, at the interface between the relational source, so the discharge source, and the first accelerating, which is either an RFQ or the thing which is ejecting the site control.
STFC-RAL-CR03 R61: We can pick off protons, at energies above 10 MeV,
STFC-RAL-CR03 R61: Our baseline capture energy is 15 MeV, that's 240 times the energy that you typically get from a discharge source.
STFC-RAL-CR03 R61: And if you remember, the space charge forces are going at the… going at the power… they scale with the power of the energy. You can see that we can pack a lot more charge into our bunch than we can with the convection scores.
STFC-RAL-CR03 R61: We can make very, very short bunches, so between 10 and 14 nanoseconds in the length of the beamlines that we've got.
STFC-RAL-CR03 R61: And our baseline 2% energy spread, specification. So,
STFC-RAL-CR03 R61: That means that we can shoot intense bunches of charge, which are quite short, we can stretch them, of course.
STFC-RAL-CR03 R61: And since this beam on demand, when you trigger the laser, you get the beam alone delay later, we can get a triggerable, arbitrary bulge structure, and we can do pump probes issues and things which haven't been possible before.
STFC-RAL-CR03 R61: So then we're obviously building this for the future. We don't want to have enormous, energy-consuming, expensive magnets.
STFC-RAL-CR03 R61: We want to use electron plasma lenses, so that would be using an electrostatic force coming from the… that's a gas of electrons, which is going to focus the particles. That changes, a 5-ton
STFC-RAL-CR03 R61: solenoid into a… into an object that, two or three people could…
STFC-RAL-CR03 R61: Yeah. So we want to use buzz within focusing.
STFC-RAL-CR03 R61: Because it gives a short focal length for a small magnetic field, and about 60 kV, electric field.
STFC-RAL-CR03 R61: And has the same effect as the solvent language. And then we want to keep this flexibility in the bunch structure, so we pick the fixed field.
STFC-RAL-CR03 R61: automating gradient accelerator, so an FFA.
STFC-RAL-CR03 R61: That has large dynamic apertures, so we can do multiple iron species. It's rapid acceleration.
STFC-RAL-CR03 R61: So they can preserve the bond structure. And, in order to have a modest-sized facility, we've chosen broken energies, specified broken energies between 15 and 127 MeV.
STFC-RAL-CR03 R61: And iron energy per nucleon from 5 to 34.
STFC-RAL-CR03 R61: anything. So that's the specification.
STFC-RAL-CR03 R61: A while back, we simulated the performance that we thought we could get with,
STFC-RAL-CR03 R61: state-of-the-art commercial later, and then, which I'm going to show you in a moment.
STFC-RAL-CR03 R61: And this is the performance that we got from the accelerator. So you can see, for proton beams at 12, 15 MeV, and the fully accelerator, 127 MeV, and 33.4 MeV carbon, you can see the dose per pulse, and then the instantaneous dose, and the average dose.
STFC-RAL-CR03 R61: Remembering that 40 grains per second is the, is the flash… threshold for,
STFC-RAL-CR03 R61: You're supposed to remember for flash. You can see we can deliver flash doses in arbitrary time structure. Now that's the specification, so as we change the design.
STFC-RAL-CR03 R61: You have to come back to find that we can deliver that set of doses.
STFC-RAL-CR03 R61: Okay, so I'm going to try and show you the stages of the studies, and,
STFC-RAL-CR03 R61: I'm really taking results from the Consent Design Report, which is all but read. The editor, Joseph, she's… she's ill, so we're not quite finished.
STFC-RAL-CR03 R61: So it's an almost final draft.
STFC-RAL-CR03 R61: We have to update the author list, actually, because the other new colleagues would like to join us. So that, I think, let's say January, that will be finished, and we'll be able to…
STFC-RAL-CR03 R61: show you all the design. I want to put the open argument in at this point, because obviously I'm presenting the work of all the collaboration.
STFC-RAL-CR03 R61: I just want to point out the collaborating institutes are running from clinical
STFC-RAL-CR03 R61: oncologists, preclinical researchers, all the way to laser plasma theory. So, really, that's an important
STFC-RAL-CR03 R61: Aspect of what we've done.
STFC-RAL-CR03 R61: Right.
STFC-RAL-CR03 R61: So,
STFC-RAL-CR03 R61: To produce the protons, we want… our baseline at the moment is that we're going to use target normal sheath acceleration.
STFC-RAL-CR03 R61: But what happens in that case is you shoot the laser in.
STFC-RAL-CR03 R61: It's an intense, so you put a dual of nasal energy.
STFC-RAL-CR03 R61: into 25 seconds, and you focus it down to a few microns in size. That means that the electric fields
STFC-RAL-CR03 R61: which are coherent because it's a laser at the time when it hits some material, so this would be a metal or a plastic foil, are very, very large. That means that the electrons, close to the surface are accelerated.
STFC-RAL-CR03 R61: They're moving in the field, some are driven into the surface, where the ion is.
STFC-RAL-CR03 R61: The ionization electrons fuel the fields as well, and they get accelerated
STFC-RAL-CR03 R61: Through the material, ionizing as they go, and they, the electric fields are such that the electrons emerge at velocities which are close to the speed of light.
STFC-RAL-CR03 R61: They recede from the surface very, very rapidly, they make a very large electric field, and they pull off
STFC-RAL-CR03 R61: positively charged objects which are sitting on the surface. So, for example, if there would be oils or hydrocarbons sitting on the surface, the protons are poured away, and eventually.
STFC-RAL-CR03 R61: The electrons are being pulled back by the positive charge, eventually the protons are leaving, and that's what points will be.
STFC-RAL-CR03 R61: I've just put in the figure from the original paper from Nature, where they're around 1 MeV equals to a peak of protons, and that was the start of the field of, of,
STFC-RAL-CR03 R61: Creating… Broke on the bees from… Related resources.
STFC-RAL-CR03 R61: Obviously, the field has evolved, and obviously there's lots and lots of work going on to increase the…
STFC-RAL-CR03 R61: laser power, and the rep rate, and produce, targets such that the energies of the product's coming up are much larger. I think the record energy now is a tool.
STFC-RAL-CR03 R61: In excess of 100 MeV.
STFC-RAL-CR03 R61: So all of that is an active field.
STFC-RAL-CR03 R61: And I guess from the Lava point of view, we want to exploit the, exploited.
STFC-RAL-CR03 R61: Development's a secret.
STFC-RAL-CR03 R61: Okay, so our R&D objectives, then, is we have been developing
STFC-RAL-CR03 R61: Towards a full-tail test of, of a source in the conditions we want to have at.
STFC-RAL-CR03 R61: The, we have specified 10Hz, and,
STFC-RAL-CR03 R61: About a joule of energy, and we don't have all of those conditions at the moment, but at least we can make the, we can get close.
STFC-RAL-CR03 R61: So…
STFC-RAL-CR03 R61: Anyway, so the tests which are closest are actually at SCAP1, I'm going to show you those in a minute. We're focused on the diagnostics and targetry development, because we need to have efficient production of particles, and we need to know what we produce. We want to have a high repetition rate, our specification is 10 Hz, but we would exploit higher…
STFC-RAL-CR03 R61: higher rates if we could get them, so we want to be able to demonstrate running at high rate for long times. And we want to be able to have codes which we benchmark against measurement, so that we can simulate the performance,
STFC-RAL-CR03 R61: It'll be moving shortly.
STFC-RAL-CR03 R61: Here's an example of some simulations that have been done.
STFC-RAL-CR03 R61: comparison of data. So, the spectrum of protons that you get off a laser-driven source with TNSA has a feature that it falls in an exponential manner until it comes to some endpoint where the flux is dropping rapidly to zero.
STFC-RAL-CR03 R61: So in this case, you can see simulations, of…
STFC-RAL-CR03 R61: As a function of the angle at which the target strikes later strikes the target, going 0 degrees to 45 degrees, and you can see that, you can either have a slow fall-off,
STFC-RAL-CR03 R61: Very good. Adjust the rate of the decrease and the height.
STFC-RAL-CR03 R61: And the position of the imported by changing the way in which the laser is striking the target. You can also look at the intensity of the laser and the thickness of the target, and we're trying to do those simulations.
STFC-RAL-CR03 R61: At the moment.
STFC-RAL-CR03 R61: A particular thing is about stability.
STFC-RAL-CR03 R61: So these are some early results from SCAPA.
STFC-RAL-CR03 R61: So what you're seeing on the pictures is a laser preparation area in this big vacuum tank.
STFC-RAL-CR03 R61: In the octagon here, the beam is forced to focus on the target, and then there's instrumentation, which is sitting inside the octagonal vacuum channel, which is looking at, both the laser spot and measuring the, the proton spectrum, which is coming up.
STFC-RAL-CR03 R61: So here, what you're seeing is the endpoint as a function of shot number, and I'm inviting you to look at the fact that the spread of the endpoint
STFC-RAL-CR03 R61: is, stable at the level of 5% or so. So, it's very important that we would be able to control the flux which is coming, and therefore, this 5% variation is something which is very encouraging.
STFC-RAL-CR03 R61: I'm gonna rapidly show you the plasma lens development.
STFC-RAL-CR03 R61: So…
STFC-RAL-CR03 R61: What we want to do is use something called a Gamble lens. That's really a gas of electrons.
STFC-RAL-CR03 R61: You put the electrons inside a pending trap, so there's a solenoid.
STFC-RAL-CR03 R61: Which is confining the electrons in the transverse plane.
STFC-RAL-CR03 R61: We put that in a potential well by putting electrodes at each end so that the electrons are confined in the neutral direction. The electrons are doing some helical motion of being reflected from the potential barriers in each end.
STFC-RAL-CR03 R61: We made a prototype, which had various problems, and the beeline that we simulated has 7 of these, as well as which
STFC-RAL-CR03 R61: Capture the beam, and then turn it into a parallel beam, which is focused that we can transport into the, the biological end station.
STFC-RAL-CR03 R61: Okay, so, how do you do that? Well, the… if you… You've seen alpha.
STFC-RAL-CR03 R61: experiment at CERN, these guys have checked that antihydrogen falls at the same rate as hydrogen should. And they've done that by having a penning trap which confines positrons, and then they slow antiprotons down in order to shoot them into the trapped positron.
STFC-RAL-CR03 R61: And these guys are the experts on, trap.
STFC-RAL-CR03 R61: low-mass states, so, track Positrons, and they're working with us now to develop the electrolytron form.
STFC-RAL-CR03 R61: Varn.
STFC-RAL-CR03 R61: In Swansea, there's a… there's what they call the polystone bean line.
STFC-RAL-CR03 R61: So what that is, is a penny trap, which I'm trying to indicate here.
STFC-RAL-CR03 R61: They have a cylindrical electrode, which they've broken up in, into different pieces so that they can
STFC-RAL-CR03 R61: But, they can make different kinds of shapes of the potential.
STFC-RAL-CR03 R61: That's all wrapped in a solenoid, so from that black line to that black line, there's a solenoid, and inside that, there's a cylindrical electrode. There's two helmet coils at the end, which are there to shape the fluid. So they have a penny trap, and they have a flexible penny trap that they can arrange by changing the electrodes.
STFC-RAL-CR03 R61: Okay.
STFC-RAL-CR03 R61: The way they operate for alpha at CERN is in this region here. They routinely store, for very long period, positron plasmas or electron plasmas, which have
STFC-RAL-CR03 R61: Order 10 to the 13 particles.
STFC-RAL-CR03 R61: cubic meter. And if you use that as a lens, then your focal length will be in the sense of a kilometer, so that's not really what we want.
STFC-RAL-CR03 R61: Our performance means that we want to have a focal length of order a meter, and that means we have to have a few times 10 to the 15 as the electrical intensity. The research program that
STFC-RAL-CR03 R61: this set of people is following us to go from the routine place here up to that, gold Polaro. I think what they would say to you is that each of the conditions
STFC-RAL-CR03 R61: But they need to do that has been achieved on its own, but not… not yet together.
STFC-RAL-CR03 R61: Right, so here's, the states of what they have been able to do.
STFC-RAL-CR03 R61: This is the functional position along the trap. What seems to be very important is that the shape of the potential is such that some ions are trapped alongside the electrons which are trapped on either side.
STFC-RAL-CR03 R61: The effect of that appears to be that the gas which is trapped in this area is providing electrons, which keeps the electron density high in the regions where the electrons are being trapped.
STFC-RAL-CR03 R61: And as a function of the trapped depth, so the degree to which, there's a, there's an essential well electrodes are sitting in, you can look at the, intensity, so you can measure the number of electrons in the traps.
STFC-RAL-CR03 R61: And it dropped off each.
STFC-RAL-CR03 R61: So with other conditions specified, they are looking at the density as a function of track voltage. We need to be up in this region here, and with the density… sorry, with the voltage source that they have at the moment, they're able to track
STFC-RAL-CR03 R61: These numbers, so the 400 getting it to 1 times 10 for the 15, so a few… only a factor of a few less than what we need.
STFC-RAL-CR03 R61: What we need to do is plot this, extension of this line, and whether we can
STFC-RAL-CR03 R61: By increasing the voltage, trap greater density of electrons.
STFC-RAL-CR03 R61: And then, of course, there's the problem of stabilizing that to make it into a lens.
STFC-RAL-CR03 R61: Our colleagues in Dentistry have been looking at the engineering of this.
STFC-RAL-CR03 R61: There's a… there's a technical problem, because the vacuum you need in the… in the… in the penny trap has to be very good.
STFC-RAL-CR03 R61: When the laser is striking the target, this here produces a lot of debris in the stuff which is pushed out of the target by the laser.
STFC-RAL-CR03 R61: So the vacuum in the source area is poor, and this is a very good vacuum, so we've had to design some, re-entrant nozzle system in order to have differential pumping, and the complexity of that area, I think you get from those drawings, and that's,
STFC-RAL-CR03 R61: That's really, I felt that from the colleague from Danson.
STFC-RAL-CR03 R61: Right, we want to accelerate the beam rapidly, so we need to design for the mixer and automating gradient accelerator. I pick out a cartoon of it here. There are 10 cells.
STFC-RAL-CR03 R61: They're, there are large return yokes hosting
STFC-RAL-CR03 R61: the, magnet. The magnet has a main dipole, a little bit like ICD light, so there's a main dipole, and then there are a set of trim quads which make the field shape such that the radius excursion as the beam is accelerated is limited.
STFC-RAL-CR03 R61: And…
STFC-RAL-CR03 R61: Once that's set up to a particular energy field is fixed, the acceleration is rapid, and, we're able to do multiple iron species acceleration. We can extract a variety of energies, which is the key specification. We can have a high repetition rate, because we're not filling them out and emptying them again, and it's got a very large acceptance.
STFC-RAL-CR03 R61: So we're able to have a large amount, a large… P.
STFC-RAL-CR03 R61: So the optics have been done, so on the… these are, if you like, typical cross, as a function of distance around the ring and the theta functions, and this is the X prime versus X, so that's the base space, which you're transporting.
STFC-RAL-CR03 R61: Key factor is the design of the manga, so Savin Crow, has simulated an opera
STFC-RAL-CR03 R61: To design the magnets, and so he has a consistent design that he's writing up in his thesis at the moment.
STFC-RAL-CR03 R61: Okay, so we think we have the design from the pixel accelerator.
STFC-RAL-CR03 R61: Right, now, back to the, back to the range verification. We have to be able to measure in real time where did the dose go. By definition, at the Bragg peak, you're not producing any signal. There's no nuclear processes happening because the programs are going too slowly.
STFC-RAL-CR03 R61: The techniques that people use in order to prompt the energy decomposition is either they use to prompt photons, which are coming from nuclear processes.
STFC-RAL-CR03 R61: People have used PET, so closed from emission tomography from, isotopes, which it created along the path.
STFC-RAL-CR03 R61: Both of these things take time to integrate photons, and they both, are exploiting the nuclear processes that happen when the beam has significant energy.
STFC-RAL-CR03 R61: So, in all those cases, you don't measure at the blank peak.
STFC-RAL-CR03 R61: By contrast, if you look at the acoustic signal which is generated by the shock wave, which is produced by an intense short pulse.
STFC-RAL-CR03 R61: striking the tissue, then you're getting the signal from the back peak, and you're able to, really reconstruct what you want to do. And you do that with acoustic sensors, which,
STFC-RAL-CR03 R61: in your hope would be outside, so they would be on the surface of the passion, and…
STFC-RAL-CR03 R61: We tried to make a proof of principle experiment. I'll show you…
STFC-RAL-CR03 R61: Well, I'll show you a cartoon of the results in a minute. What we made is a cube, and it had a re-entering system so that we could shoot the beam, either from a cyclotron or from a laser-driven source, into water. The beam energy being low means that the, distance that it penetrates is relatively small.
STFC-RAL-CR03 R61: If you look at the energy position, so, simulated Michelle, the transverse plane, you get a small dot, and then you can see the flag peak in the energy positioning on the X and Y plane, and that's what we're trying to reconstruct acoustically.
STFC-RAL-CR03 R61: We did experiments at Cytron in Birmingham, but also at the data in Munich, at LMU. So on the left-hand side, I'm showing you the normal acoustic signal.
STFC-RAL-CR03 R61: So this is the noise that comes from the laser, and the acoustic signal is here.
STFC-RAL-CR03 R61: So this is what we're processing. We'll have to find the magnitude of the
STFC-RAL-CR03 R61: Energy from the acoustic signal.
STFC-RAL-CR03 R61: We were using liquid scintillator so that we could measure the optical response and correlate the two things. I think we can understand the liquid scintillator, but the optical system has been quite difficult to reconstruct.
STFC-RAL-CR03 R61: The cube that I showed you before is indicated in front of the accelerator. This is the end of the vacuum chamber. We've got two cameras viewing the acousticulator, and two acoustic sensors listening to the acoustic response.
STFC-RAL-CR03 R61: The reason why I haven't shown you the data is because we're trying to publish it, and we don't understand the beam well enough yet. So, please invite me back, and I'll show you that. Right.
STFC-RAL-CR03 R61: College in Daresbury have laid it out. We've also tried to work out costing. This is a rendered diagram. This is, roughly speaking, 70 meters long and 35 meters wide. It's two storeys, and there's a roof with solar panels to try and
STFC-RAL-CR03 R61: in vitro radiation biology is happening on the first floor, so the vertical bends at the end of the beamline, and after the FFA to serve the two in vitro end stations. We've conceived an in vivo end station at the, on the ground floor.
STFC-RAL-CR03 R61: With good access to a rug, so that the animals can ignore taking out the animal.
STFC-RAL-CR03 R61: I want to make a point about the end station, and I'll play the video, which comes from Rosanna, in order to do that.
STFC-RAL-CR03 R61: So we need to have an act of it. The costing that we've got at the moment is that it will cost $235 million.
STFC-RAL-CR03 R61: That means that now the science has to happen all day, every day. The uptime, like solar ice or whatever, has to be 95%. So it means that your experiment, which comes after my experiment, has to be done efficiently. That handover has to be efficient. You may want different environmental conditions or different,
STFC-RAL-CR03 R61: A variety of different… things in your experiment than mine. Do we have to automate?
STFC-RAL-CR03 R61: So this is automation at the car building level, not really at the, picking something out of the rack and putting it
STFC-RAL-CR03 R61: So… There's a whole business about the end station. How do you measure? How do you measure,
STFC-RAL-CR03 R61: between pulses which are separated by less than a second, and how do you efficiently move from one experiment to another? So the whole business of the end station, the instrumentation, is as important as the accelerator, and we've only scratched the surface. Like, we know we have to do it, we haven't worked.
STFC-RAL-CR03 R61: And I think, on the campus here, working with the RFI would be a very logical thing to try and do.
STFC-RAL-CR03 R61: Right.
STFC-RAL-CR03 R61: I'm probably over time, am I?
STFC-RAL-CR03 R61: Claiming assessment. Proof of principle expert.
STFC-RAL-CR03 R61: 10 minutes? Oh, really? Okay. I'll still go quite quickly. So,
STFC-RAL-CR03 R61: So, if you like, this is really the development of the last year.
STFC-RAL-CR03 R61: We've got a great plan, if you like. There's a self-consistent,
STFC-RAL-CR03 R61: design for the facility, and now, is it better? Can you do the science that we're trying to…
STFC-RAL-CR03 R61: We're arguing for…
STFC-RAL-CR03 R61: So we've had the opportunity to try and build a proof of principle experiment based on the Scottish center for the Applications of
STFC-RAL-CR03 R61: of lasers, but I can't remember what the PA is. So this is in Straskell University in Glasgow.
STFC-RAL-CR03 R61: Poplar is a proof of principle
STFC-RAL-CR03 R61: laser… lasers for radiology or something, can't remember.
STFC-RAL-CR03 R61: So what we have done is made a quadrole-focused beamline at the end of the proton source on this capital laser.
STFC-RAL-CR03 R61: Distressed client.
STFC-RAL-CR03 R61: So there's just two points. This has been done in various spaces, including LMU.
STFC-RAL-CR03 R61: What you do is you're going to produce a spot here, if you have a perfect system, and…
STFC-RAL-CR03 R61: Okay.
STFC-RAL-CR03 R61: So this is a blown-up version of the photo that I showed you before. This is the laser preparation area. This is the target area, which is sitting inside the octagon. Out of the octagon, you're extracting the protons. There's instrumentation, and eventually the cell division, which is sitting on the animal.
STFC-RAL-CR03 R61: Then… Okay, so that's a detail of the end part.
STFC-RAL-CR03 R61: What we are doing is extracting from the main vacuum chamber, transporting the beam in this region here that's either diagnostics, or that's where we put the cell.
STFC-RAL-CR03 R61: The laser that we've got, we had a test run in last summer, into September.
STFC-RAL-CR03 R61: This was a particular shot on the screen, which is at the end where the cells would go. So you can see the focus that we've got is typical of the quadrupole, in that it's… it's across.
STFC-RAL-CR03 R61: We were using foils in order to make the green more uniform.
STFC-RAL-CR03 R61: This is the flatness of the response, so if you look at the different conditions, you can see the spread. They're not perfect, but still quite stable.
STFC-RAL-CR03 R61: The degree to which you understand the beeline, I'm trying to indicate with this.
STFC-RAL-CR03 R61: Slide, so we had,
STFC-RAL-CR03 R61: two different setups. They're distinguished by how far apart the quadrupes are.
STFC-RAL-CR03 R61: If you look at the data on the…
STFC-RAL-CR03 R61: So, yes, the data on the right, and the simulation on the left.
STFC-RAL-CR03 R61: I'm inviting you to compare the simulated result with the measurement in both
STFC-RAL-CR03 R61: For these two configurations, and I'm wanting you to conclude that we do understand the beamline reasonably well.
STFC-RAL-CR03 R61: So then we've irradiated some cell issues.
STFC-RAL-CR03 R61: Because, the energy of the beam is more than 10 MeV, we've had to make a bespoke form of, radiation dish, cell… self-container. These are glass rings, there's a mylar color plate, and I think it's got the liquid falling out, which is…
STFC-RAL-CR03 R61: This fun, arrangement there. That sits in a carousel, so there are 12 holes here.
STFC-RAL-CR03 R61: When we were doing the irradiations, there were… there were a series
STFC-RAL-CR03 R61: Of cell holders, and then, each time two.
STFC-RAL-CR03 R61: Radio chromic culture that we can monitor the beam.
STFC-RAL-CR03 R61: In situ.
STFC-RAL-CR03 R61: I'm gonna show you some test irradiations that were done in Balmio, so… The system was developed.
STFC-RAL-CR03 R61: in Birmingham, and we proved we could use it. So this is, cells grown
STFC-RAL-CR03 R61: In this case, not irradiated. The clubs are things where you count the number of cells
STFC-RAL-CR03 R61: We're going to look at my cell death, rate of cell death, and this is irradiated for me.
STFC-RAL-CR03 R61: There are different markers that can be used.
STFC-RAL-CR03 R61: So this is what's called a comet assay. So they, you radiate the…
STFC-RAL-CR03 R61: If you irradiate the cells, you break the membrane, and the proteins are leaking out. So you're able to observe that in a particular biological assay.
STFC-RAL-CR03 R61: We have… we have such measurements, so we did the irradiation.
STFC-RAL-CR03 R61: Those cells went from, Glasgow to Birmingham, I think just after Christmas.
STFC-RAL-CR03 R61: And, I have not seen results from that experiment yet, so…
STFC-RAL-CR03 R61: But I'm hoping that the radiations we've done will be it would be possible to…
STFC-RAL-CR03 R61: That we will be able to show that we can, measure…
STFC-RAL-CR03 R61: So, response, just as you did in the circuitry.
STFC-RAL-CR03 R61: Right, so that's where we are now. We've got to work out how we take the…
STFC-RAL-CR03 R61: the thing forward. So,
STFC-RAL-CR03 R61: What I wanted to do is really reflect on how we can develop the program between 36.
STFC-RAL-CR03 R61: Right, so the same slide as we had before, 3 main thrusts that we have to follow.
STFC-RAL-CR03 R61: I just pasted in, Things… Which…
STFC-RAL-CR03 R61: So this is about focusing, so that's the galvolence. We have to do the rapid acceleration. We have to do the source and the capture, and your colleagues are working on the source in any case. Instrumentation…
STFC-RAL-CR03 R61: is vital. At the moment, I think the biggest weakness of the activity at SCAPA from a natural sciences point of view is that we're not really master of the instrumentation, so that's something which we really have to develop.
STFC-RAL-CR03 R61: very energetically, and we need to be doing this under biology. I think an important thing is the development of the codes, which are there to interpret the data, so that's like, JLP4. There are JLP4-based codes, but I think that's important.
STFC-RAL-CR03 R61: I think if that worked.
STFC-RAL-CR03 R61: Right.
STFC-RAL-CR03 R61: So we need to build the activity going forward. So the collaboration has conceived a workshop series where we want to engage with the relevant peer groups.
STFC-RAL-CR03 R61: I'm working with the IOP. The IOP is considering sponsoring a series. What was new to them was the concept of a workshop series that was targeted at a particular thing, as opposed to a workshop-style meeting.
STFC-RAL-CR03 R61: And they're still worrying about…
STFC-RAL-CR03 R61: They're going to co-sponsor. But anyway, so we are making a series of workshops. We'll start with the
STFC-RAL-CR03 R61: We're calling it the Particle Therapy International meeting, where we're going to look at a deep approach to the kind of research that we want to do.
STFC-RAL-CR03 R61: And to get a full deployment for that. Then I think we're moving into more technical areas, so cylindric symmetric strong focusing of beams, so this would be plasma lenses and other beams.
STFC-RAL-CR03 R61: Novel, time-resolved, high-resolution imaging, so this is critical for the interstation. It has to be designed in from the beginning.
STFC-RAL-CR03 R61: And then we need to be looking at the… I think that's a year's program, which is outlined on that slide.
STFC-RAL-CR03 R61: The first one is now set. It's on the 27th… 27th of February 26th.
STFC-RAL-CR03 R61: change that before I give it to you. It's actually at Imperial, so it's in the surroundings on the Fleming building at Imperial, and you can see the rubric here. What we want to do is produce a short document after this, which outlines the consensus of the, of the clinicians and the preclinical researchers that we get for that meeting.
STFC-RAL-CR03 R61: That's a… that's, if you like, an important piece of groundwork that you need to do.
STFC-RAL-CR03 R61: Okay, then we need to raise the money.
STFC-RAL-CR03 R61: Okay, so this is a… This is a challenge, I guess we all know it's a challenge.
STFC-RAL-CR03 R61: We've agreed amongst the collaboration that we're going to partake of portfolio, but I'm not sure we really know what that means. But what I think the effect of it is that we're going to seek money from wherever we can get it.
STFC-RAL-CR03 R61: Which is logical. I think that UKRI, or Research Council, this is fundamental to making it work. We have to create the conditions for baseline findings coming from the Research Council, and we can enhance it with very exciting.
STFC-RAL-CR03 R61: But I think the key thing we need to do as a collaboration, and as institutes within the collaboration, is make a business plan.
STFC-RAL-CR03 R61: The collaboration has to have a business plan which is able to encompass all the business plans of the different institutes. The institutes have to have almost match that activity onto their institutes. I've written one through Imperial.
STFC-RAL-CR03 R61: I'd be happy to show it to you, but I would remind you that all projects is I've got, and it builds up the period. I guess you would expect that. I think it's fundamental that there's… there's… there's one for SDFC, and I think SDFC has a particular role
STFC-RAL-CR03 R61: Because it's the National Laboratory.
STFC-RAL-CR03 R61: And, because of the two sites, and because of the ways in which the expertise across the two sites is…
STFC-RAL-CR03 R61: exists. So, I think CDR is the springboard. We've almost got the CDR
STFC-RAL-CR03 R61: Our next collaboration meeting is in April, and I hope we're discussing the Lara business plan at that meeting.
STFC-RAL-CR03 R61: We've got to make the case, okay? 2025, we did the Great Exhibition Road Festival of Science. That led to the invitation to present… make the same presentation when President Macron visited the, the Imperial to sign an AI,
STFC-RAL-CR03 R61: activity between France and UK, and there was the open day here, open economy group, Open Lab, and we've made the same presentation there. This is really important.
STFC-RAL-CR03 R61: what I think I want to draw your attention to is that at the Green Exhibition Road Festival, which is the main picture, we were explicitly doing this with,
STFC-RAL-CR03 R61: a key industrial partner, which is Neo Cancer Care.
STFC-RAL-CR03 R61: They are key because, they want… they are marketing, or they have developed this vertical patient position system. If you want to get them into the gantry, which is fundamental to making it an order, you have to have a way of supporting a patient which is not supine, not lying down. So I think they are key partners.
STFC-RAL-CR03 R61: This year, we have a stand at the Ross Cycle Summer Science Exhibition in June.
STFC-RAL-CR03 R61: And,
STFC-RAL-CR03 R61: We lucked out on the crew, really. Good ministers and stuff were there, but we were able to make the case.
STFC-RAL-CR03 R61: This is a very important event, so,
STFC-RAL-CR03 R61: Obviously, the other people growing up.
STFC-RAL-CR03 R61: Right.
STFC-RAL-CR03 R61: So… This is now really the end. We want to use, doing profile views.
STFC-RAL-CR03 R61: In a hybrid system, where we have novel or state-of-the-art accelerator systems in order to really target the biology of cells.
STFC-RAL-CR03 R61: To do that, we've created the Lana Collaboration, and I think
STFC-RAL-CR03 R61: through the CDL, through the funding from STFC and UKRI, you really now
STFC-RAL-CR03 R61: We build on that and have the opportunity to deliver our initiative.
STFC-RAL-CR03 R61: Deliver a systematic radiation mileage program, proves the feasibility of laser hybrid acceleration, and lay the foundations of transformation with clinical practice.
STFC-RAL-CR03 R61: Sorry, convenient.
STFC-RAL-CR03 R61: Thank you. Any questions?
STFC-RAL-CR03 R61: matching from the desk?
STFC-RAL-CR03 R61: Yes, please. I've got one question around the collaboration. I saw when you put up the logos, I noticed a few universities in the NHS. Are you also both…
STFC-RAL-CR03 R61: medical, device manufacturers and the people that are actually then supplied by the unit that they involve? So, on the slide that I showed you, so it's got to be updated now we've done the CDR, because that redefines the optimist. There's Maxella, which is a software company, CoraRange, which is a software company, any sort of company,
STFC-RAL-CR03 R61: But the key partner now is Leo Cancercare.
STFC-RAL-CR03 R61: And I think we want to build that,
STFC-RAL-CR03 R61: We wanted to build on that, so if we can make concrete relations and then do something, not just trade shows, if you want, then we could reach out further. But for that to be, like, for the moment before.
STFC-RAL-CR03 R61: Yeah, totally.
STFC-RAL-CR03 R61: just to say, you could find… I have, you know, the big manufacturers.
STFC-RAL-CR03 R61: It is… scale, it's just… the difference is too big. Leo is an enemy, and the discussion is much more.
STFC-RAL-CR03 R61: Okay, let's talk. The facility you mentioned at the end, the $250 million, maybe I missed it in this slide. What was the latest?
STFC-RAL-CR03 R61: What was it, laser underneath?
STFC-RAL-CR03 R61: That was the… that was the 10 Hz, 1J, one that we… the one which is…
STFC-RAL-CR03 R61: Who's got it? I think it's…
STFC-RAL-CR03 R61: like the Lion laser or the scaffold. Oh, okay. So it's modest. Yeah, 100 terawatt scale rather than… Yes, and we haven't updated that. We chose that laser in 2020. We haven't updated it because,
STFC-RAL-CR03 R61: We want to be able to buy. Like, that's not our… we're not the guys that are selling this.
STFC-RAL-CR03 R61: You probably have to add an extra $100 billion to… There you go.
STFC-RAL-CR03 R61: Maybe a follow-up question to Gray7,
STFC-RAL-CR03 R61: We're using 100 kilowatt laser, and then he was saying, okay, as a baseline.
STFC-RAL-CR03 R61: For 10-15s, those of 10 grayish kind of region.
STFC-RAL-CR03 R61: Is it for 10th grade, so that's it.
STFC-RAL-CR03 R61: For that kind of dose, you may need, like, more focal laser there, like, parabol class system. If you get a 10-15 MeV dance of gray, because, again, with the classic couple of fuel system, like Scarpa or other 100 terabyte system, you may generate 10-15mAV,
STFC-RAL-CR03 R61: But it's exponentially the gained spectrum. Right. The floods would be quite low at 1050 region. You see what I mean? Right. So, I cut out those…
STFC-RAL-CR03 R61: No, I'm not going to try and find it. So the estimates that we've got is 10 to 9 particles is what we have based those estimates on. So I hear what you say, we absolutely have to measure that.
STFC-RAL-CR03 R61: The first time we were out there comparing our simulation to data is at SCAP.
STFC-RAL-CR03 R61: And those… those simulations are not looking like they're totally…
STFC-RAL-CR03 R61: So it's critical, yeah, delivering the program isn't critical. At the moment, I've got no reason to believe that analytics is not right.
STFC-RAL-CR03 R61: Which is a weaker word of saying what they are.
STFC-RAL-CR03 R61: But it's crazy.
STFC-RAL-CR03 R61: Any other questions? Well, you've got this workshop in February, where you're intending to write a document laying out the key advantages.
STFC-RAL-CR03 R61: Can you leap ahead and summarize what you think that, sort of, one or two main key advantages are? Well, so obviously, this is my opinion, as a natural smoker. I think there are two.
STFC-RAL-CR03 R61: One is, the short pulse, so the huge… the charge density, essentially, in our geomet.
STFC-RAL-CR03 R61: And that means that the dose of pulse is enormous.
STFC-RAL-CR03 R61: And the second is the arbitrary time structure.
STFC-RAL-CR03 R61: So, if you can map it onto conventional accelerator technology, it's like a LINAC flexibility.
STFC-RAL-CR03 R61: Let's make these small bunches, but they're low charge per bunch.
STFC-RAL-CR03 R61: So, like, we get one… it's a Linac-style bunch, but it's got a cyclotron-style charge.
STFC-RAL-CR03 R61: And we're able to do it in,
STFC-RAL-CR03 R61: We're able to do it in a triggerable.
STFC-RAL-CR03 R61: The triggerable is clearly a key issue. So if you… why do you go up the gantry? Well, partly it's history, partly because you didn't think you could do it in a… by having people up, right? Partly, it's because you want to shoot from many angles to reduce normal tissue damage.
STFC-RAL-CR03 R61: But to get in large doses of tube.
STFC-RAL-CR03 R61: So if we're able to do the reconstruction… so what has changed in 50 years? People have AI… Google, if you look at their website, can have complicated sets of people, with each of them hugging each other, and they get their hands with the right person. It is phenomenal what they can do with the image books.
STFC-RAL-CR03 R61: So the whole image processing has changed, computing has changed, both in algorithm and in hardware, so there's high-throughput hardware, which would be
STFC-RAL-CR03 R61: We could use for that. And so, the direction of travel has to be that the machine makes the decision.
STFC-RAL-CR03 R61: Do you shoot? Oh, that wasn't quite where I wanted it. So the next one is better.
STFC-RAL-CR03 R61: And that's a big development in itself, because you're…
STFC-RAL-CR03 R61: You've got to prove to Detroit.
STFC-RAL-CR03 R61: Yeah, I… Sorry, and the other angle is, it wasn't entirely clear to me why you needed to redo or go back to the cell biology, kind of… Oh, because it… so…
STFC-RAL-CR03 R61: Like you, I spent my career avoiding beams and, you know, interlock systems, and…
STFC-RAL-CR03 R61: And to have a treatment based on the data that I showed you to them, Find it.
STFC-RAL-CR03 R61: distressing, you know, somehow it's… it works, right? So the treatments work, but if you could, so, at the moment.
STFC-RAL-CR03 R61: So we abstract, so natural scientists say, we make a measurement, and then we abstract what we understand from that measurement, and we make a prediction for something else. The way the radiation biologists are working is that they have a… they do a set of experiments, which are very complicated.
STFC-RAL-CR03 R61: And they infer what the pathway is for a particular set of… for an endpoint and a particular thing that you've done.
STFC-RAL-CR03 R61: Adam.
STFC-RAL-CR03 R61: There doesn't seem to be the principle that allows you to abstract from that and predict what would happen in a different
STFC-RAL-CR03 R61: situation. So that makes it a very long process, because you have to elucidate each part of it.
STFC-RAL-CR03 R61: Plus the measurements themselves, essentially done by graduate students. So, preparation, The radiation, the post-processing.
STFC-RAL-CR03 R61: So it means that if you read the biology papers, 600 beats is a big deal, because… no, I'm serious, because that's, you know, and what we need to do is to move from that to 100.
STFC-RAL-CR03 R61: So the statistical variation needs to manage.
STFC-RAL-CR03 R61: I mean, clearly the better data on that helps everybody plan, but it's not clear to me why you can't see without it. I mean, it feels like it might be helpful. I mean, that's why there are two things from the argument for people.
STFC-RAL-CR03 R61: But if you… if you… if you want to…
STFC-RAL-CR03 R61: I mean, Ken wants to sleep well at night. Yeah, sure. Wouldn't it be nice if it was… if it was totally predictable?
STFC-RAL-CR03 R61: So, size is one thing.
STFC-RAL-CR03 R61: So just to paint the picture, somebody at some point got an MRI… developed the MRI scan and such that it would fit on the line.
STFC-RAL-CR03 R61: Now you can take it to the valleys of Wales and…
STFC-RAL-CR03 R61: article being therapy is not going on a lorry, but it could get into a distribution. No, that's clear. So then, now, if you want to do the… if you want to make it really precise, then it's about the feedback and the measure.
STFC-RAL-CR03 R61: And so now you've got to… you've got to make the measurements, but you've got to be able to interpret.
STFC-RAL-CR03 R61: And that's… that's why the data is important, so that you can build the model.
STFC-RAL-CR03 R61: So we want to understand them more. We want to, you know.
STFC-RAL-CR03 R61: And then be worried about how we break it.
STFC-RAL-CR03 R61: As opposed to having sex, which is…
STFC-RAL-CR03 R61: late 60s. I guess what I'm saying is I would be happy to do it without the biology side, demonstrate they could deliver doses, do damage to other structures in places.
STFC-RAL-CR03 R61: Point.
STFC-RAL-CR03 R61: Oh, okay.
STFC-RAL-CR03 R61: I'm not right, but I'm still uncomfortable.
STFC-RAL-CR03 R61: I think what we found in other fields, just on a similar topic, is that you get buy-in from those communities. So, like, if you're showing R in my RCF, I get those.
STFC-RAL-CR03 R61: well, if you do it in a cell, you actually get to talk to the biology scientists directly and get their engagement on the project. I think what Ken's built here is a huge collaboration with those other partners.
STFC-RAL-CR03 R61: I think that's the aspect of…
STFC-RAL-CR03 R61: At least when we've done it, not at this scale, that's what we've… that's why we've reached out. The other thing… the other sort of intellectually possible outcome
STFC-RAL-CR03 R61: You basically build it, you demonstrate that immunotherapy, your chemotherapy, you're way better, and you don't need this, it's too expensive, too complicated, too hard to run, you need too many experts.
STFC-RAL-CR03 R61: Great, so that's been something which is valuable.
STFC-RAL-CR03 R61: Even though it's negative.
STFC-RAL-CR03 R61: So, I mean, somehow that fundamental way of trying to happen to be involved with the pattern.
STFC-RAL-CR03 R61: Speaking of building it, what's sort of a realistic or ambitious timeline for that sort of… Well,
STFC-RAL-CR03 R61: So correlated with resource, so that's… and sustainability resource.
STFC-RAL-CR03 R61: But what Neil Bliss, before he retired, he thinks it's a 7-year project.
STFC-RAL-CR03 R61: I think that there's a… there's, what we need…
STFC-RAL-CR03 R61: Now, is the pre-construction R&B experience.
STFC-RAL-CR03 R61: And, so that's…
STFC-RAL-CR03 R61: Well, we wrote it down. So we wrote down a program which was over 4 calendar years.
STFC-RAL-CR03 R61: And it was… had a value of $30 million.
STFC-RAL-CR03 R61: So the next step is at the level of, let's, let's call it 3 million a year for 5 years, and then…
STFC-RAL-CR03 R61: And then you'd have a much better idea about how you would stop.
STFC-RAL-CR03 R61: And if you could email it to Sydney, To about 15.
STFC-RAL-CR03 R61: Yeah, so the…
STFC-RAL-CR03 R61: So there, in making the business plan, and beginning to discuss the collaboration business plan, I think you could look at it in this way. In the 2040s, you're able to make the case for a clinical system.
STFC-RAL-CR03 R61: Okay? That means that in the 2030s, you have to be building this, and you have to be demonstrating this.
STFC-RAL-CR03 R61: And that means that, it's what I just said, what we need now is pre-construction only. So the peer group meetings is about getting
STFC-RAL-CR03 R61: That… getting the cohort, the, what am I trying to say? All the stakeholders, To understanding the opportunities.
STFC-RAL-CR03 R61: And then you've got to plan on, right?
STFC-RAL-CR03 R61: Because maybe there's a gotcha.
STFC-RAL-CR03 R61: Do you think there's a fundamental, like, lack of understanding? Like, what do you think is the barrier there? No, well, no, because we've simulated it also, so I, I think you have to do something, you know, you have to do the R&D, but I think it can be done. You give me the opportunity to make a point which happens.
STFC-RAL-CR03 R61: But the, $205 million is our estimate. Each system is probably 20…
STFC-RAL-CR03 R61: Okay, so let's say we can't do the source with performance and reliability. Well, okay, so what we do, with less performance, less flexibility, is we have a discharge source, we have an RFQ, and maybe a couple of juicy blue macs. And we…
STFC-RAL-CR03 R61: Rescue the biological for clinical performance of the facility, and the cost, which is in order 10 to 15 million.
STFC-RAL-CR03 R61: Okay, that's a manageable service. You can put that costing into the project.
STFC-RAL-CR03 R61: To the extent that we're developing technologies which could be used for particle physics in the future, or,
STFC-RAL-CR03 R61: I'll post proton beams in the future.
STFC-RAL-CR03 R61: It's a manageable scale of risk, but still a manageable scale of risk. Whereas FCC,
STFC-RAL-CR03 R61: the points of refugee in the room. That has a conservative set of technology, because managing the risk in the way that I just help has its cost, which is
STFC-RAL-CR03 R61: Beyond the money.
STFC-RAL-CR03 R61: But at least an FCC saves lives.
STFC-RAL-CR03 R61: No, not… it wasn't an argument against FCC. It's, it's a… it's an argument that our thing, particle… I think it's not being a particle physics, needs a set of vehicles where we can develop high technical risk.
STFC-RAL-CR03 R61: On that note, could you remind us if there would be another presentation by the commercial collaborators, or…
STFC-RAL-CR03 R61: Here in my view. Yes, yes.
STFC-RAL-CR03 R61: I don't see any questions, so let's close, the seminar, again.