SBIR-STTR Award

Particle therapy is a technique for treating solid tumors that is potentially more precise than x-ray radiation therapy. Charged particles enter the patient at relativistic speeds, depositing increasingly more dose as they come to rest inside the patient. X-ray photon beams deliver an exponentially decaying dose along the beam path, dosing healthy tissue before and after the tumor. When patient alignment is accurate, proton therapy causes less collateral damage overall, delivering less dose to proximal tissue and sparing distal tissue altogether. Today, patients are positioned by matching bony structures in daily x-ray images to planning CT volumes acquired days (or weeks) prior. Inter-fraction changes to soft tissue (weight loss, edema) are common and intra-fraction changes (digestion, respiration, etc.) are unavoidable. Range errors incorrectly dose healthy tissue and undertreat the tumor, limiting benefits of proton therapy. Therefore, the American Society for Therapeutic Radiation Oncology currently supports proton therapy for tumors near the base of the neck, spine, eye and in pediatric patients, and only in the context of clinical trials for most other tumor sites. Thermoacoustic range verification relies upon stress confinement and is suitable for compact synchrocyclotrons recently introduced by two manufacturers. My lab was the first to overlay thermoacoustic range estimates onto ultrasound images of the underlying morphology using a single transducer array to ensure inherent co-registration. The work was performed at national laboratories using low energy beams that generated high frequency thermoacoustic emissions which could be detected by ultrasound imaging arrays. The next step is developing a thermoacoustic range verification prototype for particle therapy systems that pulse delivery of high energy (200 MeV or more) particles. Range straggle smooths the Bragg curve and bandlimits thermoacoustic emissions below the sensitivity band of ultrasound imaging arrays. Therefore, low frequency receivers that can detect low-frequency (DC-100 kHz) thermoacoustic emissions will be added to higher frequency (1-15 MHz) biplane ultrasound imaging arrays. Phase I will be devoted to developing a prototype that overlays thermoacoustic range estimates into a 3D visualization of orthogonal biplane ultrasound images. Thermoacoustic range estimates will be updated at a rate of 10 Hz, assuming dose is delivered sufficiently quickly. If successful, deployment of a clinical prototype for low-risk studies to collect thermoacoustic data during the normal course of treatment will follow in Phase II.

Public Health Relevance Statement:
Ion therapy concentrates dose in a small treatment "spot" and can minimize collateral damage to nearby healthy tissue - if treatment is targeted accurately. Therefore, verifying that dose is delivered to the tumor, rather than nearby healthy tissue is critical, but not yet well addressed by today's range verification techniques. A thermoacoustic range verification prototype that overlays range estimates onto ultrasound images of the patient during treatment will be developed.

Project Terms:
Acoustics; Acoustic; Anatomy; Anatomy Qualifier; Anatomical Sciences; Anatomic structures; Anatomic Structures and Systems; Anatomic Structure, System, or Substance; Anatomic Sites; Anatomic; bone; Charge; Clinical Study; Clinical Research; Clinical Trials; bowel movement; Defecation; Digestion; Hydrops; Dropsy; Edema; Electromagnetic; Electromagnetics; Elements; Equipment Failure; Eyeball; Eye; Gases; Gelatin; Goals; Heterogeneity; Ions; Laboratories; liver tumor; hepatic tumor; hepatic neoplasm; hepatic neoplasia; Hepatic Neoplasms; Liver neoplasms; Motion; Neck; Patients; Prostatic Neoplasia; Prostate Tumor; Prostate Neoplasms; Prostatic Neoplasms; treatment with radiation; radio-therapy; radiation treatment; Radiotherapy; Radiotherapeutics; Radiation therapy; respiratory mechanism; Respiration; Rest; Risk; Safety; Ships; biological signal transduction; Signaling; Signal Transduction Systems; Intracellular Communication and Signaling; Cell Signaling; Cell Communication and Signaling; Signal Transduction; Societies; backbone; Spine; Spinal Column; Vertebral column; Stress; Synchrocyclotron; Time; Body Tissues; Tissues; Transducers; ultrasound scanning; ultrasound imaging; ultrasound; sound measurement; sonography; sonogram; diagnostic ultrasound; Ultrasound Test; Ultrasound Medical Imaging; Ultrasound Diagnosis; Ultrasonogram; Ultrasonic Imaging; Medical Ultrasound; Echotomography; Echography; Ultrasonography; wt-loss; body weight loss; Weight Reduction; Weight Loss; Body Weight decreased; Work; X-Ray Medical Imaging; X-Ray Imaging; Roentgenography; Radiography; Diagnostic X-Ray Radiology; Diagnostic X-Ray; Diagnostic Radiology; Conventional X-Ray; Diagnostic radiologic examination; Xrays; X-Rays Radiation; X-Rays; X-Radiation; Roentgen Rays; Measures; Photons; Custom; Imagery; Visualization; base; Organ; Ultrasonic Transducer; Ultrasound transducer; Distal; Site; Chronic; Clinical; Phase; Medical; psychologic; psychological; Ensure; soft tissue; Radiation Oncology; Glare; Radiation Therapist; Radiotherapist; Solid Neoplasm; Solid Tumor; Therapeutic; Spottings; Morphology; Deposition; Deposit; Transrectal Ultrasound; Physiologic pulse; Pulse; proton therapy; millimeter; Frequencies; Event; Techniques; System; 3-Dimensional; 3D; 3-D; Location; Tumor Volume; American; particle; treatment planning; Speed; Structure; proton beam; Positioning Attribute; Position; Manufacturer Name; Manufacturer; Diameter; Caliber; Address; Dose; Data; Minimal Risk Study; Radiation Oncologist; Update; Development; developmental; Image; imaging; cone-beam computed tomography; volumetric computed tomography; volume computed tomography; volume CT; cone-beam CT; cost; innovation; innovative; innovate; prototype; tumor; Institutional Review Boards; IRBs; IRB; pediatric patients; child patients; particle therapy; imaging system; targeted imaging; Tissue imaging; Bone structure; skeletal structure; Patient imaging

Particle therapy is a technique for treating solid tumors that is potentially more precise than x-ray radiation therapy. Charged particles enter the patient at relativistic speeds, depositing increasingly more dose as they come to rest inside the patient. X-ray photon beams deliver an exponentially decaying dose along the beam path, dosing healthy tissue before and after the tumor. Proton therapy causes less collateral damage, and when patient alignment is accurate, delivers less dose to healthy proximal tissue and spares distal tissue altogether. Today, patients are positioned by matching bony structures in daily x- ray images to planning CT volumes acquired days (or weeks) prior. Inter-fraction changes to soft tissue (weight loss, edema) are common and intra-fraction changes (digestion, respiration, etc.) are unavoidable. Range errors incorrectly dose healthy tissue and undertreat the tumor, limiting benefits of proton therapy. Therefore, the American Society for Therapeutic Radiation Oncology currently supports proton therapy for tumors near the base of the neck, spine, eye and in pediatric patients, and only in the context of research studies for most other tumor sites. Thermoacoustic range verification relies upon stress confinement and is suitable for compact synchrocyclotrons recently introduced by two manufacturers, IBA and Mevion. A prototype system has been validated for use with IBA systems and the same receive chain has been validated for Mevion. System design for a thermoacoustic range verification (tARV) device will be finalized and validated during Phase II. The tARV consists of a wireless ultrasound array around which six thermoacoustic receivers are packed. A compact (65mm x 55mm) data acquisition (DAQ) board provides 56-59 dB gain over the thermoacoustic frequency range of 10-100 kHz, samples at 500 ksps to minimize aliasing of high frequency noise, and stores data to a secure data card onboard. A compact gamma detector monitors beam intensity and provides a trigger to the DAQ. End-to-end validation requires software integration with the treatment planning system (TPS) software used in radiotherapy clinics. Furthermore, QA and clinically realistic test objects, called phantoms, are required. Thermoacoustics is a hybrid technique that combines aspects of ultrasound imaging and radiation therapy. Commercial phantoms designed for ultrasound imaging have not yet been vetted for radiation therapy. We will integrate software, quantify materials in ultrasound phantoms already produced by CIRS, Inc and add dosimetric capability to enable end-to-end validation in a clinical environment.

Public Health Relevance Statement:
Ion therapy concentrates dose in a small treatment "spot" and can minimize collateral damage to nearby healthy tissue - if dose is targeted accurately. Therefore, verifying that dose is delivered to the tumor, rather than nearby healthy tissue is critical, but not yet well addressed by today's ion therapy systems. During Phase II, Acoustic Range Estimates will finalize design and validate a wireless thermoacoustic range verification system that computes range estimates and acquires ultrasound images of the patient during treatment.

Project Terms:
Acoustics; Acoustic; Anatomy; Anatomic; Anatomic Sites; Anatomic structures; Anatomical Sciences; Charge; Computer Systems; computing system; cost effectiveness; Defecation; bowel movement; Digestion; Edema; Dropsy; Hydrops; Electronics; electronic device; Environment; Equipment Failure; Eye; Eyeball; Gases; Gelatin; Goals; Medicare; Health Insurance for Aged and Disabled, Title 18; Health Insurance for Disabled Title 18; Title 18; health insurance for disabled; Hybrids; Intestines; Intestinal; bowel; Ions; Kidney; Kidney Urinary System; renal; Lead; Pb element; heavy metal Pb; heavy metal lead; Liver; hepatic body system; hepatic organ system; Magnetic Resonance Imaging; MR Imaging; MR Tomography; MRI; MRIs; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; NMR Imaging; NMR Tomography; Nuclear Magnetic Resonance Imaging; Zeugmatography; Monte Carlo Method; Monte Carlo algorithm; Monte Carlo calculation; Monte Carlo procedure; Monte Carlo simulation; Motion; Neck; Noise; Pancreatic; Pancreas; Patents; Legal patent; Patients; Radiotherapeutics; Radiotherapy; radiation treatment; treatment with radiation; Radiation therapy; Research; respiratory mechanism; Respiration; Rest; Ships; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Signal Transduction; Societies; Software; Computer software; Spinal Column; Spine; backbone; Vertebral column; Stress; Synchrocyclotron; Testing; Time; Tissues; Body Tissues; Ultrasonography; Echography; Echotomography; Medical Ultrasound; Ultrasonic Imaging; Ultrasonogram; Ultrasound Diagnosis; Ultrasound Medical Imaging; Ultrasound Test; diagnostic ultrasound; sonogram; sonography; sound measurement; ultrasound imaging; ultrasound scanning; Universities; Washington; Body Weight decreased; Weight Loss; Weight Reduction; body weight loss; wt-loss; Roentgen Rays; X-Radiation; X-Ray Radiation; X-ray; Xray; Photons; Treatment Cost; Uncertainty; doubt; Caring; Custom; base; Organ; detector; radiation detector; improved; Distal; Site; Chronic; Clinical; Phase; soft tissue; Radiation Oncology; analog; Funding; Solid Tumor; Solid Neoplasm; Collaborations; Imaging Phantoms; Therapeutic; Spottings; Morphology; Deposit; Deposition; proton therapy; Frequencies; Clinic; Protocol; Protocols documentation; Techniques; System; Clampings; Closure by clamp; American; particle; Performance; success; vapor; treatment planning; dosimetry; Hydrogels; Speed; Structure; research study; Devices; proton beam; Position; Positioning Attribute; Modeling; Sampling; Manufacturer Name; Manufacturer; Address; Dose; Data; multi-modal imaging; multi-modality imaging; multimodality imaging; Multimodal Imaging; Validation; Monitor; Image; imaging; cone-beam computed tomography; cone-beam CT; volume CT; volume computed tomography; volumetric computed tomography; software systems; design; designing; clinical efficacy; innovation; innovate; innovative; data acquisition; prototype; tumor; Secure; 3D Print; 3-D print; 3-D printer; 3D printer; 3D printing; three dimensional printing; pediatric patients; child patients; particle therapy; experimental study; experiment; experimental research; Cost efficiency; bundled payment; Patient imaging; Data Store; wireless; X-Ray Medical Imaging; Conventional X-Ray; X-Ray Imaging; Xray imaging; Xray medical imaging; conventional Xray; ultrasound