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When a picture is worth a thousand words: Leveraging medical imaging in clinical trials.

Medical photography can deliver a broad range of information about investigational medicinal products (IMPs) and devices. In early phase clinical trials, it can be used to gain insight on mechanism of action and clinical pharmacology. In later phase trials, medical photography can be used to assess, quantify, and monitor response to treatment. It can be tailored to document study processes and procedures and to record both subjective and objective efficacy data. Medical photography may even enhance both care delivery and patient education.

The availability of inexpensive, easy-to-use, high-quality digital cameras has increased the utilization of digital images for diagnosis and treatment monitoring. But digital cameras are just one of many devices used for medical photography. In fact, the spectrum of imaging modalities available to support and enhance clinical trial endpoint data is as broad as the array of treatment options available.

In this article, we touch upon the myriad potential applications of medical photography and explore key considerations for use of these highly technical imaging techniques in clinical trials.

What is Medical Photography?

“Medical imaging” is an umbrella term for a broad range of technologies used to create visual representations of the body for diagnosis, monitoring, or treatment of medical conditions. “Medical photography” is a general term for any data represented by a visual arrangement of pixels, which may originate from a smart phone, video camera, 3D scanner, or dedicated medical imaging devices.

Medical photography encompasses a range of imaging modalities with a variety of capabilities — enlarging microscopic detail, using filtration to visualize what cannot normally be seen with the naked eye, or employing lighting to emphasize surface detail, colour characteristics or other features. These techniques can also be combined with systems that add a temporal element to the image, whether it is capturing a fleeting moment in time and/or showing a time lapse.

The Many Modalities of Medical Photography

A wide number of techniques and technologies are available for capturing medical photographs and below are some options for incorporating their use in clinical trials.

Photomicrography. Alfred Francois Donne, a French bacteriologist widely known for his discovery of Trichomonas vaginalis, was the inventor of the photoelectric microscope and the first to apply photography to the examination of microscopic preparations in the mid-1800s. As its name suggests, photomicrography uses a microscope to record detail at greater than life size.

Ultraviolet (UV) photography. This imaging technique records details or features that are not visible to the human eye. In dermatology, for example, UV photography can be utilized to visualize subcutaneous skin damage.

Near-infrared photography. This type of photography can be used to visualize the vessel structure beneath the skin surface.

Far-infrared, or thermal, photography. This technique is most commonly used to identify fluctuations in blood flow and inflammation.

High-speed photography or video. This capture option is useful for recording events that occur too quickly to be observed by the naked eye.

Time-lapse photography or video. This technique allows unperceivably slow changes to be sped up and clear trends to be observed.

Schlieren photography. This type of photography records changes in the refractive index of a transparent medium, which can be useful for recording the flow of gases or liquids as they mix or move around objects.

Retinal imaging techniques. This capture option utilizes dedicated imaging devices to record retinal or choroidal detail. Available techniques include sodium fluorescein angiography, indocyanine green angiography, red-free photography, stereo photography, and scanning laser ophthalmoscopy.

3D or 4D imaging. These systems vary in size and method of data acquisition and may use multiple images, projected patterns, or laser scanners for 3D reconstruction. Devices range from compact cameras to specialized ulcer measurement devices, such as the AranzMedical Silhouette and 360⁰ full-body imaging systems like the 3dMD. 3dMD also offers temporal-4D motion systems that can be used to evaluate, measure, and quantify changes in anatomical function, movement, posture, and expression.

Dedicated imaging systems. Customized imaging systems can be constructed by employing specific capture methods and filtering the visual spectrum to meet client-specific requirements. Skilled medical photographers can use different combinations of light source and filtration to identify, control, or highlight characteristics of a particular area of interest. These systems must be validated with respect to their intended use.

Applications for Medical Photography

Medical photography has diverse applications across many specialties, including dermatology, pathology, psychiatry, and radiology. With ongoing advancements in technology, the potential uses for medical photography continue to expand. Common applications of medical photography include:

  • Confirmation of diagnosis
  • Assessment for surgical intervention
  • Objective measurement of morphological change throughout a treatment cycle
  • Assessment of adverse effects
  • Outcomes evaluation

Increasingly, video is being used for monitoring of patients and IMPs. Because they capture movement, expression, and even neurological responses, videos enable investigators and clinicians to conduct a broader array of observations about a patient’s health and well-being. Video is also valuable for documenting patient-reported outcomes (PROs) and ensuring that PRO assessments are delivered in a standardized and unbiased fashion.

The use of medical photography may also be an attractive differentiator from the perspective of potential study participants. In a survey on the use of medical photography in dermatology, nearly 90 percent of patients indicated that photography enhanced their quality of care. In another survey of patients presenting to an oculoplastics clinic at a tertiary eye care centre, nearly 70 percent of respondents felt that medical photography positively impacted their understanding of their illness.

Considerations for the Use of Medical Photography in Clinical Trials

Understanding the Regulatory Framework

In the United States, FDA has published a guidance document on Clinical Trial Imaging Endpoint Process Standards, which provides recommendations on important image acquisition, display, archiving, and interpretation standards when using imaging to assess a primary clinical trial endpoint. According to this guidance, the clinical trial design and context determine the importance of trial-specific imaging process standards. In some studies, it may be sufficient to simply describe these standards in the clinical protocol. When the imaging process standards are more detailed, an imaging charter may be required. This charter describes the clinical trial imaging methodology, including technical details of the imaging modality, processes for image interpretation, and procedures for image archiving.

In the EU, there is no specific guidance on imaging endpoints or standards. However, the EMA does provide guidance on the validation and qualification of computerized systems used in clinical trials and source file sharing which is relevant for digital images.

In the UK, the Institute of Medical Illustrators is the governing body for all hospital illustration or photography departments. The General Medical Council provides detailed guidance on making and using visual and audio recordings of patients. The guidance includes eight key principles designed to ensure patients’ privacy, dignity, and right to make or participate in decisions about how recordings are used.

Obtaining Informed Consent & Ensuring Confidentiality

As with any other study procedure, medical photography requires informed consent. The consent should detail the process and frequency of image capture and describe how the images will be used both during and post study. It should also explain how confidentiality will be protected.

Understanding Patient Preferences

While smartphones are ubiquitous, patients may prefer that a hospital-owned camera be used.

Selecting an Imaging Endpoint

When contemplating imaging as an endpoint, researchers should first consider if it is standardized, precise, and accurate. They should also make a determination as to whether it has sufficient clinical meaningfulness for use in submissions to support regulatory approval.

Handling Variability

Like any other data point in a clinical study, photos and videos are subject to variability. In a clinical trial setting, variability in the imaging equipment, materials, and processes involved may result in increased variability in endpoint measurements, ultimately impacting the achievement of trial objectives. To ensure image consistency and reproducibility, the equipment, camera settings, participant positioning, lighting, and photography technique all should be standardized. Where possible, capture techniques and processes should be validated against established reference targets or analysis parameters.

Researchers will also need to determine whether images will be interpreted at the site, at a centralized facility, or at both locations. Use of a central reader may be beneficial in studies in which site-based variability or bias are anticipated. For example, in open-label trials in which clinical information might influence interpretation, centralized image interpretations may also be advisable when specialized reader training is required. Importantly, using a central reader may improve efficiency, cost, and data quality as image assessment is performed on an ongoing basis, rather than only at the end of the study.

Ensuring Image Quality

Medical photography must capture patient and disease characteristics in a manner that is accurate, reproducible, and interpretable. Image quality is paramount, as perceived lack of quality or accuracy can affect the reader’s interpretation and conclusions and change the outcome of a study. A best practice is to structure image content so that it is clearly captured, presented, and pertinent and conveys a direct message to the observer or reader.

The use of imaging biomarkers as a primary endpoint requires use of “scientific grade” imaging data and a rigorous process for handling image variability. Scientific grade medical photographs should meet the following criteria:

  • Correct perspective
  • Inclusion of a scale aligned with the frame of the image
  • Even lighting
  • Neutral background

Momentum Behind Medical Photography

In an era in which hybrid and patient-centered clinical trials are gaining popularity, medical photography can reduce or replace in-person, on-site evaluations with off-site visits. Using standardized imaging equipment, mobile research nurses performing home visits can now capture images comparable to those acquired at the site. Advances in technology are also making medical photography more accessible and versatile and, sometimes, more affordable.

Applying artificial intelligence and deep learning to medical imaging may also jumpstart the use of medical photography. Historically, a challenge of observing and quantifying image-related associations has been the myriad patterns, colours, shapes, and other features that exist in real data. Deep learning, however, has successfully extracted new knowledge from images. In one study, deep learning models predicted cardiovascular factors – including age, gender, smoking status, systolic blood pressure, and major adverse cardiac events – from photographs of the retinal fundus. Other studies have shown the utility of deep learning in detecting diabetic retinopathy or predicting hypertension, hyperglycemia, and dyslipidemia from retinal fundus photography.

Conclusion

Medical photography can be a very powerful tool for documenting and reinforcing the safety and efficacy of an IMP or device. Researchers can push the boundaries of this highly specialized, highly technical modality by considering how imaging data via the visual spectrum and beyond can be used as clinical trial endpoints. Collaborating with a qualified and experienced medical photographer who knows the latest capture options and cost implications can help researchers identify, design, and utilize the right medical photography to support the development and approval of new drugs and devices.