tFUS Brain Imaging for Brain Cancer

Recruiting in Palo Alto (17 mi)

Overseen by David Darrow, MD MPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Minnesota

Disqualifiers: Awake craniotomy, Unhealed wounds, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Transcranial focused ultrasound (tFUS) offers a platform for non-invasive imaging and treatment of the brain and pathology of the brain -- allowing high resolution imaging in both spatial and temporal dimensions. Compared with the gold- standard for brain imaging, magnetic resonance imaging (MRI), ultrasound offers reduced contrast while providing improved sampling in time through a significantly more cost-effective approach. In addition, while MRI is used to guide invasive treatments, only ultrasound can offer treatments through three primary mechanisms: 1) neuromodulation, 2) blood brain barrier modulation, and thermal/mechanical ablation through high intensity focused ultrasound (HIFU). All three treatment options require targeting therapy through the skull, which remains a barrier to clinical translation. This proposal is to test the feasibility of acquiring noninvasive targeting imaging intraoperatively prior to clinically indicated cranial neurosurgery. By acquiring volumetric ultrasound images while coregistered to previously obtained stereotactic magnetic resonance imaging, the study will be able to compare the ability of tFUS to identify and focus on brain pathology.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Transcranial Focused Ultrasound (tFUS) for brain cancer?

Research shows that Magnetic Resonance Guided Focused Ultrasound (MRgFUS) is a promising tool for treating brain tumors by enhancing the delivery of chemotherapy and precisely targeting and destroying tumor tissue. It has been used successfully for other conditions like essential tremor and is being explored for brain cancer treatment. ^{1 2 3 4 5}

Is transcranial focused ultrasound safe for humans?

Research shows that transcranial focused ultrasound (tFUS) has been used safely in humans for various conditions, including brain tumors and neurological disorders like Parkinson's disease and essential tremor. Studies have reported successful procedures without causing neurological deficits or other adverse effects, suggesting it is generally safe. ^{6 7 8 9 10}

How does the tFUS treatment for brain cancer differ from other treatments?

The tFUS (transcranial focused ultrasound) treatment is unique because it can non-invasively target deep brain structures using sound waves, unlike traditional treatments that may require surgery or radiation. This method allows for precise targeting of brain areas without the need for incisions or exposure to harmful radiation. ^{1 2 8 11 12}

Research Team

David Darrow, MD MPH

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for adults who are scheduled for brain surgery, can give informed consent, and will be under general anesthesia. They must have detailed contrast imaging of the brain available and use neuronavigation during surgery. It's not for those with scalp wounds/infections, significant health risks as judged by the lead researcher, or pregnant individuals.

Inclusion Criteria

Able to undergo informed consent

Thin cut post-contrast imaging available for coregistration

I am scheduled for and will attend brain surgery.

Exclusion Criteria

I don't have heart or lung problems that make surgery risky.

I have open wounds or infections on my scalp.

I am scheduled for a surgery on my brain while I am awake.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline imaging and segmentation using ultrasound and MRI to assess feasibility and volume

1 week

1 visit (in-person)

Intraoperative Imaging

Noninvasive targeting imaging intraoperatively prior to clinically indicated cranial neurosurgery

During surgery

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Transcranial Focused Ultrasound (Ultrasound)

Trial Overview The study tests if transcranial focused ultrasound (tFUS) can effectively target and image brain tumors compared to MRI. tFUS may offer a cheaper alternative with better time resolution without invasive procedures like neuromodulation or thermal ablation that MRI-guided treatments require.

Participant Groups

Group I: Experimental group Experimental Treatment 1 Intervention

Participants scheduled for brain surgery

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Shashank Priya

University of Minnesota

Chief Executive Officer since 2023

PhD in Materials Engineering from Penn State

Charles Semba

University of Minnesota

Chief Medical Officer since 2021

MD from the University of Minnesota Medical School

Findings from Research

Transcranial MRI-guided focused ultrasound (MRgFUS) is an established therapy for treating essential and parkinsonian tremors, showing long-term safety and efficacy in recent studies.

The technique is expanding beyond tremors to include new indications like focal dystonia and neuropsychiatric conditions, with promising preliminary results, and it also allows for innovative applications such as opening the blood-brain barrier and neuromodulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update in the clinical application of focused ultrasound. Natera-Villalba, E., Matarazzo, M., Martinez-Fernandez, R.[2022]

Magnetic resonance-guided focused ultrasound (MRgFUS) has been shown to effectively and safely disrupt the blood-brain barrier (BBB), enhancing the delivery of various chemotherapeutic agents into brain tumors, as evidenced by preclinical studies and initial clinical trials.

The use of MRgFUS in glioma patients has demonstrated improved penetration of drugs like gadolinium across the BBB, indicating its potential to improve treatment outcomes, although further research is needed to fully understand drug distribution and effects on tumor growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Strategies for Brain Tumor Therapy. Bunevicius, A., McDannold, NJ., Golby, AJ.[2022]

Magnetic resonance guided focused ultrasound (MRgFUS) has been FDA approved for treating essential tremor that doesn't respond to other treatments, highlighting its safety and efficacy as a new intervention.

The article discusses optimization strategies for imaging before, during, and after the procedure, emphasizing the importance of effective MRI techniques to ensure successful ablation during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cranial MR-guided Focused Ultrasound for Essential Tremor : Technical Considerations and Image Guidance. Levi Chazen, J., Stradford, T., Kaplitt, MG.[2020]

Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive technique that can precisely target and treat brain disorders by creating thermal lesions and disrupting the blood-brain barrier, which is a significant advancement in neurotherapeutics.

MRgFUS has been successfully used in various clinical applications, including treating bone metastases and uterine fibroids, and is being explored as a safer alternative to traditional neurosurgery for a range of brain-related conditions, supported by studies from small animal models to large clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial applications of magnetic resonance-guided focused ultrasound. Lipsman, N., Mainprize, TG., Schwartz, ML., et al.[2021]

A systematic review of 33 studies on low-intensity transcranial focused ultrasound stimulation (TFUS) indicates that adverse effects are very rare, with most studies showing no significant negative outcomes even when safety limits were exceeded.

However, at high stimulation intensities, TFUS can potentially cause serious issues like hemorrhage, cell death, and unintended blood-brain barrier opening, highlighting the need for further research to establish clear safety guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies. Pasquinelli, C., Hanson, LG., Siebner, HR., et al.[2020]

A 63-year-old patient with a recurrent glioblastoma underwent transcranial MR-guided focused ultrasound surgery (MRgFUS), demonstrating the feasibility of this noninvasive technique for brain tumor ablation.

The procedure involved 25 high-power sonications and successfully achieved partial tumor ablation without causing neurological deficits or adverse effects, highlighting its safety and potential for treating brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound. Coluccia, D., Fandino, J., Schwyzer, L., et al.[2020]

Transcranial focused ultrasound (tFUS) can selectively target and modulate deep brain structures, such as the amygdala and entorhinal cortex, in healthy adults, leading to significant changes in brain perfusion and activity.

The study demonstrated that tFUS does not activate the auditory cortex, indicating that its effects are due to direct neuromodulation rather than an acoustic response, suggesting potential therapeutic applications for neurological and psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans. Kuhn, T., Spivak, NM., Dang, BH., et al.[2023]

MR-guided focused ultrasound (MRgFUS) is a promising non-invasive technique for treating deep brain conditions, showing effectiveness in chronic diseases like Parkinson's and essential tremor, as well as in neuropathic pain.

The method is advantageous because it does not require anesthesia, avoids ionizing radiation, and has low complication rates, making it a safer alternative to traditional neurosurgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR-guided focused ultrasound: a new generation treatment of Parkinson's disease, essential tremor and neuropathic pain. Dobrakowski, PP., Machowska-Majchrzak, AK., Labuz-Roszak, B., et al.[2021]

Transcranial focused ultrasound (tFUS) is a promising non-surgical technique for neuromodulation that offers better spatial resolution compared to traditional electro and electromagnetic methods.

tFUS can effectively target sub-cortical brain structures non-invasively, and its combination with BOLD functional MRI allows for enhanced examination of brain activity in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound for BOLD fMRI signal modulation in humans. Leo Ai, ., Mueller, JK., Grant, A., et al.[2022]

Transcranial focused ultrasound (tFUS) can be effectively planned using synthesized CT (sCT) images generated from MRI, which avoids the need for potentially harmful CT radiation, showing high correlation with real CT (rCT) images in skull measurements.

The study demonstrated that the differences in simulated peak pressure and focal locations between sCT and rCT were minimal, indicating that sCT can be a reliable alternative for tFUS treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of synthetically generated computed tomography for use in transcranial focused ultrasound procedures. Liu, H., Sigona, MK., Manuel, TJ., et al.[2023]

The dual-channel radiofrequency receive-only head coil significantly improves imaging quality in tcMRgFUS, providing up to 4 times better signal-to-noise ratio (SNR) compared to the standard body coil, which enhances visualization of critical brain structures.

The head coil also improves MR thermometry accuracy, reducing temperature uncertainty from 0.96°C to 0.41°C, allowing for more precise monitoring of thermal ablation during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of an MRI receive head coil for use in transcranial MR guided focused ultrasound for functional neurosurgery. Bitton, RR., Sheingaouz, E., Assif, B., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Update in the clinical application of focused ultrasound. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging-guided, high-intensity focused ultrasound for brain tumor therapy. [2006]

3. United States pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Strategies for Brain Tumor Therapy. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Cranial MR-guided Focused Ultrasound for Essential Tremor : Technical Considerations and Image Guidance. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Intracranial applications of magnetic resonance-guided focused ultrasound. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies. [2020]

7. England pubmed.ncbi.nlm.nih.gov

First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

MR-guided focused ultrasound: a new generation treatment of Parkinson's disease, essential tremor and neuropathic pain. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound for BOLD fMRI signal modulation in humans. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Evaluation of synthetically generated computed tomography for use in transcranial focused ultrasound procedures. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Evaluation of an MRI receive head coil for use in transcranial MR guided focused ultrasound for functional neurosurgery. [2021]