SFDI Imaging for Scleroderma

(SFDI Trial)

Overseen By Andreea Bujor, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Boston University

Disqualifiers: Skin malignancy, Wounds, Life expectancy < 5 years

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

92 Participants Needed

Trial Summary

What is the purpose of this trial?

Scleroderma (SSc) is an autoimmune disease characterized by fibrosis (or collagen deposition) of the skin and internal organs. The extent of skin fibrosis is an important predictor of internal organ complications and increased mortality. Currently imprecise and subjective methods that varies amongst different doctors for the same patient are available to quantify skin fibrosis in patients, by "pinching" their skin and assessing how thick it is; this is the method used to determine the modified Rodnan skin score (mRSS). Skin thickness and the amount of fibrosis can change over time due to disease progression or in response to therapy. In this research, longitudinal measurements will be taken to determine if spatial frequency domain imaging (SFDI) can detect changes in skin thickness that occur over time in response to therapy or from disease progression in scleroderma patients. This study will compare SFDI with other clinical outcome assessments of skin thickness and fibrosis in scleroderma patients including mRSS, skin biopsy histology, scleroderma skin patient reported outcome (SSPRO), ultrasound, and durometry (durometer measures skin hardness). SFDI information will also be compared with capillaroscopy (allows for non-invasive imaging of the nailfold capillaries) if available from the electronic medical record. If SFDI correlates well with other clinical outcome assessments, it may be used in the future as a rapid, non-invasive tool for monitoring disease activity in scleroderma patients.

Do I need to stop my current medications for the trial?

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 Spatial-frequency domain imaging (SFDI) for scleroderma?

Research shows that SFDI can detect skin changes in scleroderma patients even at early stages, providing a more reliable and objective assessment compared to traditional methods. It has a strong correlation with existing skin assessment scores and biopsy results, suggesting it could improve monitoring of disease progression and treatment effectiveness. ^{1 2 3 4 5}

Is SFDI imaging safe for humans?

Spatial Frequency Domain Imaging (SFDI) is a non-contact imaging technique that has been used safely in studies with healthy volunteers and patients with scleroderma, showing reliable results without reported safety concerns. ^{2 3 6 7 8}

How does the SFDI treatment for scleroderma differ from other treatments?

The SFDI treatment for scleroderma is unique because it uses a non-contact imaging technique with spatially modulated light to create a detailed map of skin properties, offering a more objective and reliable assessment of skin fibrosis compared to the traditional method, which relies on a physician's touch and can vary between observers. ^{2 3 4 9 10}

Research Team

Andreea Bujor, MD, PhD

Principal Investigator

BU Chobanian & Advesian School of Medicine

Eligibility Criteria

This trial is for individuals with systemic scleroderma, or those suspected of having it based on symptoms. Healthy controls without scleroderma or diseases that could affect results can also join. Participants shouldn't have skin wounds, rashes where imaging will be done, a recent skin cancer diagnosis (except certain treated cases), or illnesses with life expectancy under 5 years.

Inclusion Criteria

I have been diagnosed with systemic sclerosis.

You have been diagnosed with systemic sclerosis (SSc) by a doctor, or you have symptoms that suggest you might have SSc, or you are a healthy person without SSc or any other condition that could affect the study results.

You are free from Systemic Sclerosis or any other condition that may affect the outcomes.

Exclusion Criteria

I have been diagnosed with a skin cancer other than squamous cell, basal cell, or carcinoma in situ in the last 2 years.

I have other serious health conditions with a life expectancy of less than 5 years.

I have wounds or rashes where they plan to do skin tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial measurements including SFDI, mRSS, ultrasound, durometry, and optional skin biopsy and blood collection

1 visit

1 visit (in-person)

Longitudinal Monitoring

SFDI, mRSS, ultrasound, durometry, and SSPRO assessments every 3 months for the first 12 months, then every 6 months up to 36 months

36 months

Quarterly visits for the first year, then biannual visits

Annual Assessments

Annual skin biopsy and blood collection to evaluate histopathological changes and serum biomarkers

Annually

Follow-up

Participants are monitored for safety and effectiveness after the main study period

6 months

Treatment Details

Interventions

• Spatial-frequency domain imaging (SFDI)

Trial Overview The study tests if spatial frequency domain imaging (SFDI) can accurately monitor changes in skin thickness and fibrosis over time in scleroderma patients. It compares SFDI to current methods like the modified Rodnan skin score, biopsies, patient reports, ultrasound, durometry and capillaroscopy.

Participant Groups

Group I: Scleroderma Participants Experimental Treatment 1 Intervention

Participants in this arm will be asked to complete the Fitzpatrick skin type questionnaire to quantify skin tone and will have measurements taken with a colorimeter on the right and left forearms, hands, and fingers to quantify skin tone at the first study visit. Participants will be asked to complete the SSPRO questionnaire at the time of enrollment and every three months for the first 12 months and then every six months until the end of the study. At each study visit, a physician will measure the mRSS, which is a method of quantifying skin fibrosis; SFDI measurements, ultrasound, and durometry will then be done. Skin biopsies will be collected from the forearm of each subject annually. A small amount of blood will also be collected from subjects once per year to explore serum biomarkers of fibrosis.

Group II: Healthy controls Active Control 1 Intervention

Participants in this arm will be asked to complete the Fitzpatrick skin type questionnaire to quantify skin tone and will have measurements taken with a colorimeter on the right and left forearms, hands, and fingers to quantify skin tone at the first study visit. At each study visit, SFDI measurements, ultrasound, and durometry will be done. Skin biopsies will be collected from the forearm of each subject annually. A small amount of blood will also be collected from subjects once per year to explore serum biomarkers of fibrosis.

Who Is Running the Clinical Trial?

Boston University

Lead Sponsor

Trials

494

Recruited

9,998,000+

Fibrosis ARC: Connecting Tissues and Investigators (FCTI ARC)

Collaborator

Trials

1

Recruited

90+

Scleroderma Clinical Trials Consortium (SCTC)

Collaborator

Trials

1

Recruited

90+

Findings from Research

A new method was developed to characterize and compensate for optical aberrations in spatial frequency domain imaging (SFDI) and spectroscopy (SFDS), which are important for accurately assessing tissue properties.

The compensation technique significantly improved measurement accuracy, keeping errors in scattering to within 1.3% and absorption to within 3.8%, regardless of depth or layer thickness, enhancing the reliability of these non-invasive imaging tools.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of optical aberrations on depth-specific spatial frequency domain techniques. Majedy, M., Das, N., Johansson, J., et al.[2023]

Spatial frequency domain imaging (SFDI) offers a more quantitative and reliable method for assessing skin fibrosis in systemic sclerosis (SSc) patients compared to the traditional modified Rodnan skin score (mRSS), which is subjective and prone to variability.

SFDI was able to detect skin changes even in early-stage SSc, showing significant differences in optical properties between healthy controls and SSc patients, and demonstrated strong correlations with both mRSS scores and histological findings, indicating its potential for improved monitoring of disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spatial frequency domain imaging for the assessment of scleroderma skin involvement. Pilvar, A., Mehendale, AM., Karrobi, K., et al.[2023]

Multimodal imaging techniques, including optical coherence tomography (OCT), magnetic resonance angiography (MRA), and Doppler ultrasonography (DUS), can effectively differentiate between scleroderma (SD) patients and healthy individuals by revealing significant structural and functional changes in the skin and blood vessels.

In a study with six participants, SD patients showed thicker skin, reduced blood vessel presence, and lower blood flow compared to healthy controls, highlighting the potential of these imaging methods for early detection and diagnosis of scleroderma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining optical coherence tomography with magnetic resonance angiography and Doppler ultrasonography for clinical detection of scleroderma. Zhang, L., Li, M., Liu, Y., et al.[2021]

Spatial frequency domain imaging (SFDI) has rapidly advanced in the last decade, offering unique capabilities for imaging optical properties and chromophores across a large field-of-view quickly.

The review highlights the collaborative efforts in the SFDI community to share knowledge, including publications and freely available resources for hardware and processing, which can enhance the accessibility and application of this imaging technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spatial frequency domain imaging in 2019: principles, applications, and perspectives. Gioux, S., Mazhar, A., Cuccia, DJ.[2020]

A new compact spatial frequency domain imaging (SFDI) device was developed using a multispectral compound-eye camera, allowing for simultaneous imaging at multiple wavelengths, which can help evaluate tissue properties in low-resource settings.

The device accurately measured optical properties in tissue-simulating phantoms and demonstrated its effectiveness in a murine model of burn wounds, showing consistent changes in tissue properties that align with known effects of burn severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spatial frequency domain imager based on a compact multiaperture camera: testing and feasibility for noninvasive burn severity assessment. Kennedy, G., Kagawa, K., Rowland, R., et al.[2023]

The study demonstrated that using [18F]Sodium Fluoride PET/low-dose CT imaging can effectively visualize active calcifications in patients with systemic sclerosis, which is crucial since calcinosis cutis is often irreversible once visible.

In a pilot study of nine female patients, [18F]NaF PET detected calcifications that were not visible on conventional low-dose CT in some cases, suggesting that this imaging technique could help identify early calcification formation and guide timely interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]Sodium Fluoride PET has the potential to identify active formation of calcinosis cutis in limited cutaneous systemic sclerosis. Atzeni, IM., Hogervorst, EM., Stel, AJ., et al.[2022]

In a study of 25 children with juvenile localized scleroderma, non-invasive imaging techniques successfully distinguished between affected and non-affected skin, showing that affected skin was thinner and had higher temperature, blood flow, and oxygenation levels.

The imaging results correlated with the Localised Scleroderma Cutaneous Assessment Tool (LoSCAT), indicating that thicker, less well-perfused skin is associated with active lesions, while thinner, highly perfused skin indicates damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive imaging and clinical skin scores in juvenile localised scleroderma. Pain, CE., Murray, A., Dinsdale, G., et al.[2023]

A prediction model developed from early systemic sclerosis (SSc) patients can effectively identify 'good' and 'bad' trajectories of damage accumulation using only baseline damage index, sex, and cutaneous subset, achieving high accuracy (ROC AUC of 0.9313 for lcSSc and 0.9027 for dcSSc).

The study revealed distinct damage accumulation patterns between limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), indicating that tailored approaches may be necessary for managing these different subsets of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediction of damage trajectories in systemic sclerosis using group-based trajectory modelling. Baron, M., Barbacki, A., Man, A., et al.[2023]

The study presents a motion correction algorithm for Spatial Frequency Domain Imaging (SFDI) that significantly improves the accuracy of optical property measurements in moving skin surfaces, achieving fidelities within 1.5% of ideal stationary conditions.

Testing in real clinical conditions showed that the motion correction technique reduced measurement variance by up to 92.63%, highlighting its importance for accurately assessing skin lesions and other optical properties in a clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of motion on optical properties in the spatial frequency domain. Nguyen, JQ., Saager, RB., Cuccia, DJ., et al.[2021]

The pilot study utilized multispectral photoacoustic elastic tomography (PAET) to identify significant differences in physiological and elastic properties between the fingers of scleroderma patients and healthy individuals, suggesting these differences could serve as biomarkers for early detection of the disease.

The study involved 6 participants (3 healthy and 3 with scleroderma) and demonstrated that the quantitative measurements obtained from PAET could enhance understanding of the disease's pathological mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging molecular signatures for clinical detection of scleroderma in the hand by multispectral photoacoustic elastic tomography. Liu, Y., Zhang, L., Li, S., et al.[2019]

References

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

Influence of optical aberrations on depth-specific spatial frequency domain techniques. [2023]

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

Spatial frequency domain imaging for the assessment of scleroderma skin involvement. [2023]

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

Combining optical coherence tomography with magnetic resonance angiography and Doppler ultrasonography for clinical detection of scleroderma. [2021]

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

Spatial frequency domain imaging in 2019: principles, applications, and perspectives. [2020]

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

Spatial frequency domain imager based on a compact multiaperture camera: testing and feasibility for noninvasive burn severity assessment. [2023]

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

[18F]Sodium Fluoride PET has the potential to identify active formation of calcinosis cutis in limited cutaneous systemic sclerosis. [2022]

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

Non-invasive imaging and clinical skin scores in juvenile localised scleroderma. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Prediction of damage trajectories in systemic sclerosis using group-based trajectory modelling. [2023]

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

Effects of motion on optical properties in the spatial frequency domain. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Imaging molecular signatures for clinical detection of scleroderma in the hand by multispectral photoacoustic elastic tomography. [2019]