Advancements in Dermatological Imaging Modalities

Introduction

Every year, the field of medicine witnesses technological advancements, leading to improved patient care and furtherment of research, which contribute to the efficient acquisition of knowledge and skill by physicians and surgeons. A discipline like dermatology, which relies heavily on the recognition of morphological patterns, gains bountifully from cutting-edge technologies for capturing images, facilitating disease diagnosis, and their monitoring and progression. These novel modalities offer the potential to bridge the gap between clinical assessment and invasive procedures, reducing the need for biopsies and enhancing diagnostic accuracy.

The majority of these modalities are designed to be user-friendly and provide quicker results compared to routine histopathology.[1] They also offer the advantage of non-invasive follow-up for monitoring disease progression.[1] Nevertheless, certain modalities, such as spectroscopy, demand substantial experience in interpretation and analysis, leading to a longer learning curve.[2] However, the adoption and accessibility of these advanced technologies in India remain a challenge. Factors such as high costs, limited infrastructure, and a shortage of trained professionals contribute to the restricted availability of these modalities across the country. Some of these modalities are available in specific tertiary care institutions and medical colleges; however, their application is predominantly confined to research rather than being utilized in patient care. It is important to note that these are not confirmatory tests and may still mandate a biopsy, especially in malignant skin diseases. The legal implications of diagnosing with reflectance confocal microscopy (RCM) versus histopathology are complex. While RCM offers an innovative, non-invasive approach, its legal standing is under scrutiny. For dermatological diagnosis, the longstanding gold standard has been histopathology. Legal expectations and norms in medical practice have evolved around this traditional method, establishing it as the benchmark for legal precedents and standards in the field. Legal considerations involve RCM’s acceptance, expertise requirements, and alignment with medical standards. Practitioners must stay informed, ensuring compliance amid evolving legal discussions in technological advancements. Newer imaging modalities of interest to dermatologists are appended below.

Dermoscopy

It is also known as dermatoscopy, incident light microscopy, or epiluminescence microscopy. It is one of the most extensively utilized diagnostic tools in a dermatologist’s toolkit. It finds frequent application in diagnosing cases where the clinical diagnosis is uncertain or ambiguous as well as in evaluating treatment effectiveness. Currently, a variety of dermoscopes are available in the market, ranging from handheld devices to video-based systems. Many of these dermoscopes are equipped with built-in polarizers, enabling visualization up to the papillary dermis.[3,4]

Newer modifications of dermoscopy include the following:

1. Ultraviolet (UV) dermoscopy: It functions like an amplified Wood’s lamp, emitting UV light within the 360–390 nm range and generating fluorescence in visualized structures to assist in diagnosing various disorders.[5] In cases where dermoscopy and Wood’s lamp examination may not provide a definitive diagnosis, this technique can provide valuable additional information and clarity [Figure 1].[5] However, its higher cost compared to conventional dermoscopes currently restricts its widespread clinical use. The uses of UV dermoscopy are summarized in Table 1.[5,6,7,8,9,10] The advantages and disadvantages are summarized in Table 2.[7]

2. Infrared dermoscopy: It assists in capturing cellular activity and vascular patterns of the lesion, offering valuable indicators for distinguishing a lesion as either benign or malignant. Macro-infrared imaging is an innovative dermoscopy technique that utilizes an infrared sensor to detect temperature differences and variations in local heat signatures of small lesions.[11] Similarly, near-infrared (NIR) fluorescence in vivo imaging leverages the emission of photons within the 700–1000 nm range, which are then absorbed by tissues based on their unique absorption spectra and auto-fluorescence properties.[11] The absorption spectra of various tissues depend on their scattering properties, anisotropy, and refractive indices. The use of fluorescent dyes like indocyanine green enhances the differences in the absorption spectra, resulting in more clinically distinct tissue image profiles. The analysis of emitted photons with different wavelengths produces an image that highlights variations in local tissue perfusion, vasculature, and local enzyme activity [Figure 2].[12] The uses of infrared dermoscopy are summarized in Table 3.[12,13,14,15,16,17] The advantages and disadvantages are similar to those of UV dermoscopy.

Figure 1.

Progressive vitiligo visualised by UV dermoscopy (x20) which better delineates the perifollicular pigmentation and fuzzy borders in the depigmented macule compared to polarized microscopy (x20) (Source: Yuan et al.)[5]

Table 1.

Uses of UV dermoscopy

Diseases	Findings
Fungal infections	Characteristic fluorescence patterns (pityriasis versicolour – yellow or orange fluorescence; tinea capitis – blue-green fluorescence).[6]
Vitiligo	Identifying and evaluating the extent of depigmentation in vitiligo.[5]
Scabies	Sarcoptes scabiei can be visualized under UV light due to the presence of fluorescent substances in the mite giving bright green fluorescence.[7]
Erythrasma	UV dermoscopy can reveal coral-red fluorescence in affected areas, facilitating diagnosis and treatment.[7]
Trichobacteriosis	Yellow-green fluorescent concretions can be visualized along the hair shafts.[8]
Porphyrias	Some types of porphyrias can present with characteristic fluorescence patterns under UV light.[9]
Melasma	UV dermoscopy highlights the extent and depth of pigment distribution.[9]
Vascular tumors	Glomus tumors produce a “pink glow” on UV dermoscopy.[10]

Table 2.

Advantages and disadvantages of UV dermoscopy[7]

Advantages	Disadvantages
Enhanced visualization of certain skin features and structures	Limited standardization in interpreting UV images.
Detection of subtle changes in pigmentation and vasculature.	Limited availability
Improved contrast for better identification of specific features.	Requires specialized training and experience for accurate interpretation.
Differentiation between benign and malignant skin lesions.	Potential concerns about patient safety related to UV exposure.
May aid in monitoring progression of skin conditions over time.	Costly acquisition and maintenance of specialized UV dermoscope equipment.

Figure 2.

Infrared dermoscopy showing different patterns of malignant and borderline malignant lesions highlighting areas with different metabolic activity (Source: Ferrari et al.)[12]

Table 3.

Uses of infrared dermoscopy

Indications	Description
Vascular imaging	Enables visualization of vascular patterns and structures in vascular skin lesions, such as angiomas and vascular malformations.[13]
Diagnosis and monitoring of melanoma	Enables identification of deeper structures in melanocytic lesions. NIR dermoscopy, in particular, may reveal specific patterns that could be indicative of melanoma progression.[14]
Assessment of pigment network	Enhanced visualization of the pigment network in pigmented skin lesions.[12]
Differentiation of melanocytic and non-melanocytic lesions	Enables differentiation between melanocytic lesions (e.g., melanoma, nevi) and non-melanocytic lesions (e.g., seborrheic keratosis, dermatofibroma) based on their structural and vascular characteristics.[15]
Visualization of subsurface dermoscopic structures	Enables visualization of subsurface structures, such as blood vessels and dermal collagen.[12]
Monitoring of wound healing	Helps in monitoring of wounds by allowing assessment of vascularization and tissue changes beneath the skin surface.[16]
Assessment of inflammatory skin conditions	Offers insights into the vascular changes associated with inflammatory skin conditions, such as psoriasis and eczema.[12]
Detection of subclinical lesions	Enables the visualization of subtle vascular changes in the lesional skin, helping to identify subclinical lesions that might not be apparent on standard clinical examination or dermoscopy.[17]

Optical coherence tomography

Popular among ophthalmologists, optical coherence tomography (OCT) is an imaging modality based on the principle of interferometry. It uses near-infrared light waves and can see up to a depth of 1–2 mm, which corresponds to the reticular dermis.

Principle: This technique is analogous to ultrasound imaging but utilizes light waves in the near-infrared range, centered at a wavelength of about 840 nm, instead of sound waves.[18] It involves splitting light waves into a reference beam and a probe beam using optical fibers. The probe beam passes through the tissue being examined, while the reference beam is directed at a mirror. As the light passes through the tissue, it reflects at varying time delays based on the tissue’s optical properties and depth of structures. The light directed at the mirror returns with no time delay. Both reflected lights are combined, resulting in an interference pattern when they are in the same phase or ‘coherent.’ The phase difference between the backscattered light from the mirror and the tissue provides valuable information about the tissue’s microstructure, and computational analysis is employed to translate this delay into meaningful data for analysis.[18]

The uses of OCT include the following:

• Blistering disorders by enabling individual layer and inter-layer evaluation.[19]

• Pre-malignant lesions like actinic keratoses and Bowen’s disease show thickening of the epidermis with stronger scattering by the stratum corneum due to parakeratosis with an intact basement membrane.[20]

• Basal cell carcinoma (BCC): Neoplastic basal cells appear as dark ovoid islands, whereas deeper parts of the tumor are sharply demarcated from the dermis by a dark line (hyporeflective boundary) representing the surrounding fibrous stroma [Figure 3].[20,21]

• Hyperproliferative disorders such as psoriasis and eczema.[22]

Figure 3.

Optical coherence tomography (6 mm × 1.5 mm) (a) and corresponding histology (H and E, 50x) (b) of a basal cell carcinoma on the lower eyelid. The distribution of signal in the malignancy is more homogenous compared to adjacent healthy skin (Source: Welzel et al.)[21]

The advantages and disadvantages of OCT are summarized in Table 4.[18,19,20,21,22]

Table 4.

Advantages and disadvantages of optical coherence tomography

Advantages	Disadvantages
Higher resolution than ultrasound enabling visualization of individual layers of the skin	Limited penetration compared to sound waves resulting in visualization of only 1–2 mm depth in the skin.
Act as a bridge between high frequency ultrasound and confocal microscopy	Unable to visualize cellular details
Real-time, non-invasive, non-contrast imaging	Differentiation between basal cell carcinoma and actinic keratosis is not possible

Dynamic optical coherence tomography

It is a modification of conventional OCT used to visualize blood vessels and skin microvasculature.[23]

Principle: It utilizes multiple OCT scans to identify areas displaying image variations between consecutive scans. Since the majority of tissues remain unchanged, except for blood vessels, dynamic OCT efficiently captures cutaneous microvasculature. Despite variations in vessel characteristics across the body, normal skin consistently exhibits a well-organized vascular pattern, facilitating differentiation from diseases featuring cutaneous microvascular alteration.[23] The uses of dynamic OCT are summarized in Table 5.[24,25,26,27,28,29,30] The disadvantages are similar to those of conventional OCT.

Table 5.

Uses of dynamic optical coherence tomography (OCT)

Diseases	Findings
Basal cell carcinoma	Exhibit loss of organized vasculature, which is replaced by numerous small vessels concentrated around the BCC lesion, enhancing non-invasive detection of BCC and its boundaries.[24]
Actinic keratoses	The vasculature displays a reticular network similar to normal skin, but with larger caliber vessels and a broader network, with increased density around the adnexal structures.[25]
Squamous cell carcinoma	Contrary to the typical reticular pattern, vessels in squamous cell carcinoma appear dotted, semicircular, or fuzzy and are of larger caliber.[26]
Melanocytic naevi versus melanoma	In melanocytic naevi, the vascular network is comparable to normal skin, with a few distinctions, but in melanoma, early intradermal growth displays disorganized red dots in the superficial dermis, while invasive and thick tumors exhibit abundant, dilated, and aneurysmal vessels arranged vertically with angulated branches.[27]
Inflammatory dermatoses	Dynamic OCT can be employed to visualize various inflammatory conditions such as rosacea, psoriasis, and connective tissue disorders like scleroderma, which involve abnormal vasculature.[28,29,30]

Reflectance confocal microscopy

Confocal microscopy aims to generate high-quality images comparable to conventional histopathological images, obviating the need for invasive biopsies. This non-invasive technique effectively distinguishes benign and pre-cancerous/cancerous lesions in real time. By utilizing laser light, it enables visualization to a depth of 200–300 μm, typically reaching the papillary dermis.[31]

Principle: Confocal microscopy employs a focused beam of light with a pinhole to capture high-resolution images of skin layers, allowing specific depth imaging and real-time observation of dynamic processes like blood flow and cellular movements.[32] A laser beam is directed onto the skin through mirrors and a scanning device, while fluorescent dyes can enhance contrast to highlight structures or cells. The reflected or emitted light is collected by a detector, converted into an electrical signal, and processed by software to reconstruct detailed skin images. These images can be analyzed to assess cellular morphology, identify cell types, and evaluate tissue architecture.[32]

Confocal microscopy is an invaluable tool for dermatological research and education. It enables scientists to study skin biology, wound healing processes, and the effects of various treatments.[32,33] It also aids in teaching by providing high-resolution visualization of skin structures and conditions.

• Skin cancer diagnosis: Melanoma, basal cell carcinoma, and squamous cell carcinoma can be diagnosed by visualization of cellular and architectural features of skin lesions.[33]

• Inflammatory skin conditions: Psoriasis, eczema, and lichen planus can be diagnosed by visualizing specific cell types involved in inflammation and infiltration into lesional skin. It can also help assess treatment response, detect recurrence, and guide decision-making regarding further interventions.[34]

• Nail disorders: It can be used to examine nail disorders, including onychomycosis (fungal nail infection), nail psoriasis, and nail dystrophies.[35]

• Hair and scalp disorders: It allows for non-invasive assessment of hair and scalp disorders such as alopecia areata, androgenetic alopecia, and scalp infections.[36]

• Pigmentary disorders: It can aid in detecting the distribution of melanin, melanocytes, inflammatory cells, vasculature, and dermal changes [Figure 4].[37]

• Blistering disorders: It aids in the evaluation of the exact level of the split, its contents, and the composition of the dermal infiltrate.[38]

• Hereditary disorders: Hailey-Hailey disease, epidermolysis bullosa, xeroderma pigmentosum, Rothmund-Thomson syndrome, and certain forms of ichthyosis.[39]

Figure 4.

Melasma on the left cheek of a 61-year-old female patient. (a) Dermoscopy shows a thin pigment network with arcuate and annular structures sparing follicular openings. (b) Bright-edged papillae at the dermo-epidermal junction (DEJ) and hyper-reflective cobblestone pattern observed at the supra basal layer. The angulated, bright-edged papillae (yellow arrowhead) at the DEJ correspond to the pigment network on dermoscopy. (c) Increased keratinocyte pigmentation with few dendritic cells (red arrowhead). (d) Within dermal papillae, large oval bright structures (red circle) are seen, representing melanophages (Source: Farabi et al.)[37]

The advantages and disadvantages of confocal microscopy are summarized in Table 6.[33,34]

Table 6.

Advantages and disadvantages of confocal microscopy[33,34]

Advantages	Disadvantages
High-resolution imaging of skin layers	Costly equipment and maintenance
Non-invasive technique	Limited penetration depth (200-300 mm)
Real-time visualization of dynamic processes	Time-consuming image processing
Differentiates between benign and precancerous/cancerous lesions	Relatively slow imaging speed
Enables specific depth imaging with pinhole	Requires expertise for accurate interpretation
Reveals cellular details and tissue structures	Limited field of view
Allows topical application of fluorescent dyes for contrast enhancement	Fluorescent dyes may have potential side effects

Line-field confocal optical coherence tomography

Line-field confocal microscopy is an innovative fusion of advanced imaging modalities, creating high-resolution images that enable “in-vivo histology”.[40] By merging the strengths of conventional OCT (providing vertical images but lacking cellular characteristics) and reflective confocal microscopy (producing cellular images in a horizontal plane), this technique compensates for its limitations. With line-field illumination, it can generate precise, cell-resolved images of the skin in vertical, horizontal, and three-dimensional sections, revolutionizing the way we visualize skin structures non-invasively.[40]

It can be employed for all the applications mentioned above for both OCT and reflectance confocal microscopy, offering superior resolution and additional planes for visualization.

Spectroscopy

This technique enables the assessment of ultra-structural details in lesional skin by utilizing electromagnetic radiations of different wavelengths. Depending on the type of spectroscopy employed, it allows analysis at various skin levels.[2]

Principle: Spectroscopy employs electromagnetic radiation and involves various processes[2]:

• Absorption: Electrons or molecules transition from lower to higher energy states, corresponding to specific energy levels or molecular vibrations.

• Emission: The sample emits light at distinct wavelengths when excited by an external energy source, enabling the identification of its composition or characteristics.

• Scattering: Incident light interacts with the sample, causing light to scatter in different directions, offering information on particle size or molecular structure.

The transmitted, absorbed, emitted, or scattered light is detected using specialized sensors like photodiodes or photomultiplier tubes. The resulting electrical signal is analyzed to generate a spectrum, indicating the intensity or wavelength distribution of the electromagnetic radiation. Spectra reveal characteristic patterns or peaks, aiding in compound identification, molecular analysis, or concentration quantification in the sample.[2]

Types of spectroscopy:

The various types in various stages of application in dermatology include:

• Reflectance spectral imaging: This involves capturing images of the skin by measuring the intensity of reflected light across different wavelengths.[40]

• Fluorescence spectral imaging: It utilizes fluorescent probes or dyes that bind to specific molecules or structures in the skin. The emitted fluorescence is captured and analyzed to assess various aspects of skin health.[41]

• Polarized spectral imaging: It involves the use of polarized light to capture images of the skin. By controlling the polarization of light, this technique can reveal information about skin texture, sub-surface structures, and the presence of certain skin conditions.[42]

• Hyperspectral imaging: It captures images across a wide range of narrow and contiguous spectral bands. It enables the analysis of subtle color and texture variations that may indicate the presence of abnormalities or disease.[43]

• Infrared thermography: It involves capturing thermal images of the skin to assess temperature variations. It can be used in the evaluation of conditions such as cellulitis, vasculitis, and venous insufficiency.[44]

The uses include:

• Skin cancer detection: Alteration of sub-cellular organelle and membrane damage, seen in cancerous cells, can be evaluated, permitting earlier diagnosis of pre-cancerous/cancerous lesions.[45]

• Micro-circulation and pigmentation: The mexameter is a non-invasive device for estimating melanin and hemoglobin levels in the skin, providing the melanin index (MI) and erythema index (EI). It employs a spectrometer technique, emitting three light wavelengths to measure skin reflection. With stored calibration data, it ensures accuracy without frequent recalibration. It is useful in pigmentary and vascular disorders, like melasma and rosacea, making it a valuable tool for clinical and treatment assessment and medical surveys.[45] Other devices used to measure pigmentation include a dermaspectrometer and a chromameter.

• Used to determine the efficacy of therapeutic and cosmetic skin products, assess the penetration of active ingredients, evaluate skin hydration levels, and monitor the effects of treatments or interventions.[46]

• Allergen identification: It can also aid in allergen identification that causes contact dermatitis because different substances have unique spectral signatures.

• Research: It aids in understanding various neoplastic and non-neoplastic skin conditions and the development of drugs.[47]

The advantages and disadvantages of spectroscopy are summarized in Table 7.[48,49]

Table 7.

Advantages and disadvantages of spectroscopy[48,49]

Advantages	Disadvantages
Non-invasive procedure	High cost
Provides objective and quantitative measurements	Requires expert training
Enables assessment of skin hydration, melanin and collagen content, and sebum production	Variability in skin types can affect spectroscopic analysis
Real-time monitoring	Variability in interpretation and the lack of standardized protocols
Raman spectroscopy provides depth profiling capabilities, which are valuable for studying skin layers, evaluating epidermal-dermal junction integrity, and assessing the depth of skin lesions.	Limitations in terms of specificity: Some spectroscopic techniques may not be able to differentiate between specific skin conditions or accurately identify specific molecules or biomarkers.

Photo-acoustic imaging

It is a non-invasive imaging technique that combines the principles of laser-induced photo-acoustic effect and ultrasound detection. It uses a pulsed infrared light and can see up to 1 cm depth, which includes the reticular dermis and subcutis.[50]

Principle: A pulsed light is used to illuminate the tissue under observation. Certain components of the tissue are able to absorb the photonic energy and deposit heat in the tissue, leading to thermo-elastic expansion and producing ultrasound waves detected by transducers, which are in turn made into images using software. Using lithium niobate-based transducers, it achieves a resolution of 20 μm in the lateral dimension and 5 μm in the axial dimension through the entire skin depth.[50]

• Melanoma detection: By assessing the distribution and concentration of melanin, it can differentiate benign moles from malignant melanomas [Figure 5].[51]

• Diagnosis and margin assessment in skin cancers: It may aid in the early diagnosis of all skin cancers by identifying aberrant vascularization and may help in treatment by identifying margins for excision.[51]

• Vascular Imaging: It enables the evaluation of blood flow, oxygenation levels, and vascular abnormalities associated with conditions such as hemangiomas, port-wine stains, or venous malformations.[52]

• Psoriasis and dermatitis monitoring: It can help monitor the progression and severity of skin conditions like psoriasis and dermatitis.[53]

• Wound assessment and healing: It can assess wound healing progress by visualizing tissue oxygenation, inflammation levels, and blood vessel formation in the wound bed.[54]

• Scleroderma: It can be used for the assessment of nail fold capillaries for the diagnosis of scleroderma and other connective tissue disorders. It estimates vessel density and capillary diameter similar to conventional microscopy but more accurately and in depth as epidermal characteristics do not affect the results.[55]

• Acne and sebaceous gland imaging: It can visualize sebaceous glands and assess sebum production and distribution. It aids in studying the pathogenesis of various disorders of sebaceous glands including acne and evaluating treatment responses.[56]

• Skin aging: It can analyze skin aging-related changes, such as collagen degradation, elastin content, and tissue hydration.[57]

• Drug/cosmetic delivery and nanoparticle imaging: It can track the distribution and uptake of nanoparticles or targeted drug delivery systems in the skin. It enables the evaluation of drug delivery efficiency and provides insights into the local bio-distribution of therapeutic agents.[58]

Figure 5.

Photoacoustic images at 532 nm illumination wavelength of (a) Abdominal (i) melanoma lesion, and (ii) healthy; (b) Flank (i) melanoma lesion and (ii) healthy; (c) Bar chart of photoacoustic signal intensity. Higher signal intensity from melanoma lesion due to the presence of an increased melanin in the epidermis and, therefore, higher absorption compared to normal skin (Source: Kratkiewicz et al.)[51]

The advantages and disadvantages of photo-acoustic imaging are summarized in Table 8.[50]

Table 8.

Advantages and disadvantages of photoacoustic imaging[50]

Advantages	Disadvantages
High contrast and resolution allowing differentiation between various exogenous and endogenous chromophores	Limited availability
Functional imaging allowing real-time, in vivo evaluation of physiological processes, such as cutaneous blood flow, oxygenation, and tissue metabolism.	Photoacoustic image reconstruction can be computationally intensive and time-consuming requiring advanced algorithms and computational techniques
Non-invasive and non-ionizing	Requires expertise in operation
Deeper tissue penetration than pure optical imaging techniques	High cost
Multimodal imaging potential as it can be combined with other imaging modalities, such as ultrasound or OCT, to provide complementary information.	Lack of standardization due to variability in imaging parameters, data acquisition, and interpretation.

Time-correlated single-photon counting (TCSPC)

This technique is used to assess the penetration of substances into the epidermis and dermis. It relies on fluorescence lifetime measurement and time-of-flight imaging principles, which are relevant in skin research, though its practical utility in routine clinical practice may be limited.[59]

Principle: A detector, such as a photo-multiplier tube (PMT) or an avalanche photodiode (APD), is used to detect photons emitted or reflected from the sample, which generates an electrical pulse or signal. The electrical pulse is amplified while maintaining the time resolution. The detector signal and the timing reference signal are fed into a time-to-amplitude converter (TAC), which measures the time difference and converts it into a current signal proportional to the time delay. These signals are processed and analyzed using specialized software to extract relevant information on the intensity, lifetime, and time-related properties of the sample.[59,60]

• Fluorescence lifetime imaging microscopy (FLIM): It can provide information about tissue composition, metabolic processes, and the presence of specific fluorophores or markers, aiding in the diagnosis and monitoring of skin cancers, inflammatory skin disorders, and pigmentation disorders.[60]

• Tissue characterization: By analyzing the fluorescence lifetime and kinetics of endogenous or exogenous fluorophores, it can help distinguish between healthy and diseased tissues, identify specific cellular or molecular changes, and assess tissue viability or pathology.[60]

• Drug delivery and penetration studies: By using fluorescently labeled compounds, it tracks the fluorescence lifetimes of topical agents and assesses their delivery efficiency, permeation depth, and interaction with skin components.[61]

• Assessment of wound healing: By monitoring the fluorescence lifetimes of specific biomarkers associated with wound healing, TCSPC can provide insights into tissue repair, neovascularization, and the overall healing trajectory.[59]

• Skin cancer detection: Using the difference in fluorescence lifetimes of normal and cancerous skin.[62]

• Pathogenesis of skin disorders: Analyzing the fluorescence lifetimes of specific biomarkers or cellular components helps in better understanding at a molecular level in diseases like psoriasis, eczema, and autoimmune diseases.[63]

The advantages and disadvantages of TCSPC are summarized in Table 9.[63]

Table 9.

Advantages and disadvantages of time-correlated single photon counting (TCSPC)[63]

Advantages	Disadvantages
Real-time visualization of dynamic processes and molecular interactions.	Complex instrumentation and setup, including instrument availability, high cost, and technical expertise.
Sensitivity to low concentrations allows determination of cellular or molecular changes associated with early-stage skin diseases or subtle alterations in tissue metabolism.	Limited spatial resolution: TCSPC is often combined with other imaging techniques, such as confocal microscopy or multi-photon microscopy, to obtain spatially resolved data.
Low noise levels: Results in improved signal-to-noise ratio and accurate data.	Acquisition time: Slow acquisition times for capturing sufficient photon statistics.
Minimal photodamage and photobleaching: Suitable for studying delicate biological samples.	Current evidence is limited to research in dermatology alone with no role in routine clinical practice.

High-frequency ultrasound

High-frequency ultrasound (HFUS) is increasingly employed in modern dermatological practice. It involves the use of frequencies exceeding 20 MHz, enabling visualization of structures up to the deep fascia.[64]

Principle: It utilizes high-frequency sound waves above the audible range (typically in the range of 20–50 MHz). These sound waves are generated by a transducer, which penetrates the skin and encounters different tissue interfaces within the skin layers. At each tissue interface, a portion of the ultrasound waves is reflected in the transducer, which causes the piezoelectric crystals to vibrate, producing electrical signals. The electrical signals are processed and analyzed to form a two- or three-dimensional image of the scanned area. The depth and resolution of the image depend on the frequency of the ultrasound waves used.[64]

The uses include:

• Diagnosis, staging, and treatment assessment in skin lesions: HFUS aids in evaluating the depth and characteristics of skin lesions, such as tumors, cysts, and inflammatory conditions. It also helps determine the thickness of skin layers, useful in assessing edema, and scarring.[65]

• Margin assessment in skin cancers: For adequate excision [Figure 6].[66] Additionally, it can aid in the visualization of in-transit cancerous cells as they traverse the lymphatics and vasculature away from the site of the primary tumor.

• Assessment of vasculature: It aids in assessing vascular lesions, vascular malformations, and vascular involvement in skin tumors. Laser Doppler imaging can aid in the delineation of micro-vasculature also.[67]

• Examination of hair follicles, hair shafts, and the scalp’s structure and disorders.[68]

• Research and education: To study skin biology, wound healing, and the effects of treatments.[69]

• Nerve damage in leprosy: Assess and monitor therapeutic response by measuring nerve thickness, change in echogenicity pattern, and nerve abscesses.[70]

Figure 6.

High-frequency USG showing the presence of hyper-echoic spots (arrow) corresponding to the basaloid islands on histology (Source: Tamas et al.)[66]

The advantages and disadvantages of high-frequency ultrasound are summarized in Table 10.

Table 10.

Advantages and disadvantages of high-frequency ultrasound

Advantages	Disadvantages
Non-invasive	Low specificity
Ease of availability and cost-effective	Resolution is not comparable to histology
Improved depth of visualization: It can detect structures as deep as deep fascia.	Testing and interpretation is operator dependent leading to a learning curve.

Thermography

Cutaneous infection, inflammation, and increased blood flow are associated with changes in skin temperature. Thermography or thermal imaging is a method of measuring and visualizing thermal radiation emitted by the body or object under evaluation. It detects infrared radiation emitted by the tissues and can detect structures up to 2 mm deep.[71]

Principle: Thermography utilizes thermal imaging to measure and visualize the infrared radiation emitted by the skin’s surface.[71] By detecting and mapping these temperature variations, the technique provides valuable insights into the underlying pathophysiological processes and can aid in diagnosing and monitoring various skin disorders non-invasively.[71,72,73,74,75,76,77]

The uses include:

• Burns: To diagnose the level of burn (the deeper the burn, the cooler the lesions).[72]

• Cancers: Skin cancers have an increased temperature due to angiogenesis, differentiating melanoma metastasis from other benign skin lesions.[73,74]

• Scleroderma: Dysfunctional cutaneous blood flow in response to cold stimuli.[75]

• Morphea: Used to differentiate active lesions from inactive lesions.[75]

• Cellulite: Assessment of severity.[75,77]

• Vascular lesions: Assessment of treatment response in vascular lesions (e.g. response to laser in the port-wine stain).[75,77]

The advantages and disadvantages of thermography are summarized in Table 11.[75,76]

Table 11.

Advantages and disadvantages of thermography

Advantages	Disadvantages
Non-invasive and radiation-free	Limited depth of detection (up to 2 mm)
Rapid imaging process	Temperature variations due to external factors may affect results
Non-contact	Less accurate in areas with hair or clothing
Visualizes thermal patterns in real time	Interpretation requires specialized training

Artificial intelligence/Machine learning (AI/ML)

Artificial intelligence is causing a revolutionary impact in nearly every field imaginable. Medicine, including dermatology, is no exception to this. It holds the potential to bring tremendous benefits to the field and significantly transform healthcare practices.[78]

Principle: Data on patients with skin diseases, such as clinical images, patient records, and histopathological information, are collected and compiled to serve as the input and are used to train AI/ML models. Computer algorithms are used to learn and analyze the data to extract meaningful interpretations. The models learn to recognize color, texture, shape, patterns, shape, and so on, providing a set of differential diagnoses to work with. The more you train the algorithm, the better it gets at accuracy and performance in providing diagnoses. Various techniques, such as deep learning, convolutional neural networks (CNN), or support vector machines (SVM), are applied to develop models specifically tailored for dermatological analysis [Figure 7].[78,79]

Figure 7.

A schematic diagram showing the complex AI neural network (Source: Li et al.)[79]

The uses of AI/ML in dermatologic imaging include:

• Identification, early detection, treatment planning, and monitoring of disease progression.[80]

• Providing risk-based stratification: Higher sensitivity in recognition of pre-malignant and early malignant lesions compared to dermatologists.[80]

• Helpful to general physicians and patients in remote areas in decision-making.[80]

• Improve the training of resident dermatologists by generating complex and rare disease morphologies.[80]

The advantages and disadvantages of AI/ML-based dermatologic imaging are summarized in Table 12.

Table 12.

Advantages and disadvantages of artificial intelligence/machine learning (AI/ML) in dermatologic imaging

Advantages	Disadvantages
Enhanced diagnostic accuracy and efficiency	Dependence on high-quality and diverse datasets
Faster and automated analysis of large datasets	Potential for biased or inaccurate predictions
Consistent and reproducible results	Need for expert annotation and validation
Early detection of skin diseases	Complexity of implementing AI/ML algorithms
Assist in decision-making and treatment planning	Initial cost and infrastructure requirements
Reduction in the workload	Limited interpretability of AI/ML predictions
Potential for personalized patient care	Ethical and privacy concerns surrounding data
Improved detection of rare or subtle conditions	Challenges in integrating AI/ML into clinical workflow

Computed tomography scan

Computed tomography scan, commonly known as CT scan, is an imaging modality which uses X-rays in series, rotated around a body part to create computer-generated cross-sectional images. It is an essential investigation used in many of the medical and surgical specialties. Reliance on such imaging modalities is comparatively less frequent in dermatology.

Principle: In contrast to conventional X-ray imaging, where a fixed X-ray source is used, a CT scan employs an X-ray source that rotates around the specific body part. After completing a full rotation, the computerized machine generates a 2-dimensional image slice. By gradually moving the bed on which the patient lies, multiple such image slices are acquired and saved. These slices can be used individually or stacked together to form a 3-dimensional image of the scanned area of the body.

CT scans find applications in dermatology in the following ways:

• Staging cutaneous cancers: CT scans aid in evaluating internal organ involvement in skin cancers such as melanomas, cutaneous lymphomas, and others. While Fluorodeoxyglucose-Positron Emission Tomography is a more advanced modality commonly used for this purpose (discussed below), CT scans are crucial for assessing internal organ involvement before planning treatment.[81]

• Systemic sclerosis: In systemic sclerosis, where interstitial lung disease (ILD) is often associated, CT scans, particularly high-resolution ones, are employed for diagnosing and monitoring lung involvement. ILD can manifest as usual interstitial pneumonia (UIP) or non-specific interstitial pneumonia (NSIP). NSIP presents with features like ground glass opacities, reticular opacities, and traction bronchiectasis, with characteristic subpleural sparing, while UIP is characterized by honeycombing.[82]

• Vascular anomalies and malformations: CT scans serve as an excellent modality to assess the depth and size of vascular anomalies, playing a crucial role in determining the appropriate treatment modality. They also assist in evaluating treatment response and internal organ involvement. For instance, CT scans aid in diagnosing hepatic hemangiomas associated with cutaneous hemangiomas and assessing vascular malformations of internal organs in cases of skin-related vascular malformations. In the latter, CT angiography is typically performed.[83]

• Imaging of underlying bone in cutaneous infections: CT scans are useful for imaging the underlying bone in cutaneous infections such as mycetoma.[84]

• Calcinosis cutis and osteoma cutis: CT scans are employed to detect the location, number, and extent of calcifications in conditions like calcinosis cutis and osteoma cutis.[85]

• Evaluation of neurocutaneous syndromes: Valuable in identifying bony irregularities like optic foramen enlargement in neurofibromatosis 1 (NF 1). CT scans may be utilized to assess the existence of fat-containing renal angiomyolipomas in tuberous sclerosis. Depending on the genodermatosis, CT scans may be used to examine bony anomalies, such as lesions in the cranial or facial bones.

• The advantages and disadvantages of CT scans are summarized in Table 13.

Table 13.

Advantages and disadvantages of computed tomography in dermatologic imaging

Advantages	Disadvantages
Detailed imaging	Radiation exposure
Deep tissue evaluation	Limited soft tissue contrast
Bone assessment	Cost
Rapid imaging	Lack of real-time imaging
3D reconstruction	Contrast agent risks – Renal injury
Compatibility with other imaging	Not ideal for superficial lesions
Surgical planning	Limited soft tissue differentiation

Positron emission tomography-computed tomography scan (PET-CT)

A PET-CT scan merges positron emission tomography (PET) and computed tomography (CT) to provide comprehensive anatomical and functional information. This combination significantly improves diagnostic precision, especially in oncology, where it plays a crucial role in detecting, staging, and monitoring cancer treatments.

Principle: PET-CT involves combining two imaging modalities: PET and CT. In PET, a radiotracer, commonly fluorine-18 fluoro-deoxyglucose (FDG), is injected into the body. Metabolically active cells, such as cancer cells, absorb the radiotracer. The PET component detects emitted positrons, creating a functional image of metabolic activity. Simultaneously, the CT component provides detailed anatomical information.

• Skin cancers: Elevated concentration occurs in cells with rapid metabolism and turnover, such as cancer cells. Hence, it is employed for diagnosing, staging, and monitoring various cancers, including skin cancers.[86]

• Paraneoplastic dermatoses: Associated with internal neoplasms but not a direct manifestation of the primary tumor; paraneoplastic dermatosis requires identifying internal malignancy. PET-CT is commonly used when specific signs of internal malignancy are not overt.[87]

• Sarcoidosis: PET-CT reveals increased uptake in disorders like sarcoidosis, where macrophages and CD4+ T-cells have glucose transporters. This proves valuable in diagnostic dilemmas, especially for assessing internal organ involvement.[88]

• The advantages and disadvantages of PET-CT are summarized in Table 14.

Table 14.

Advantages and disadvantages of positron emission tomography-computed tomography scan

Advantages	Disadvantages
Both metabolic status and anatomical structure can be assessed in single scan	High cost
Useful in occult malignancies when there is minimal anatomical distortion of the body part	Risk of false positives due to non-cancerous lesions mistaken for cancer due to high metabolic activity
Highly sensitive	Radiation exposure
Diagnosis, monitoring, and treatment response can be assessed	Risk of false negatives, as certain cancers can be slow growing
Whole body imaging	Risk of hypersensitivity to radiotracers
Integration with other imaging modalities	Limited spacial resolution compared to CT or MRI scan

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a non-invasive medical imaging technique that uses strong magnetic fields and radio waves to generate detailed images of the internal structures of the body. It is particularly useful for visualizing soft tissues, organs, and joints, providing valuable diagnostic information in medical practice.[89]

Principle: MRI relies on the principle of nuclear magnetic resonance. When exposed to a strong magnetic field and radiofrequency pulses, certain atomic nuclei, particularly hydrogen protons in the body, emit signals. By analyzing the signals’ spatial and frequency information, a computer constructs detailed images of the body’s internal structures, offering excellent soft tissue contrast in medical diagnostics.[89]

The uses of MRI in dermatology include:

• Functional MRI: It enables the identification of precise areas in the brain associated with specific pathways like pain or pruritus.[90]

• Depth assessment: MRI facilitates precise evaluation of pathology size by assessing the depth of lesions and sub-clinical extensions into subcutaneous tissue or underlying muscle. Accurate measurements guide clinicians in determining the most appropriate management approach, as demonstrated in conditions like morphea and cellulite.[91,92]

• Exploration of skin physiology and anatomy: MRI can depict structures at a sub-millimeter scale in vivo, enabling the study of the epidermis, dermis, and subcutis. It provides detailed visualization of various skin appendages and allows assessment of interactions among structures and water-macromolecular interactions. Additionally, it permits quantification of water-lipid content.[93]

• Evaluation of pre- and post-intervention changes in pathology: MRI enables precise delineation of volume alterations in lesions following interventions such as cold knife removal, reduction with energy-based devices, or embolization. This information assists clinicians in targeting lesions effectively, maximizing the reduction in pathology size while minimizing side effects.[94]

• Evaluation of neurocutaneous syndromes: Crucial for examining neurofibromas, optic gliomas, and other manifestations in the central nervous system. It assists in pinpointing the location, size, and extent of neurofibromas, particularly those involving cranial nerves in neurofibromatosis 1 (NF 1). In tuberous sclerosis, it is instrumental in detecting cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs), offering detailed insights into associated brain and renal lesions. Valuable for evaluating neurological involvement in diverse genodermatoses, such as Sturge-Weber syndrome, aiding in the visualization of leptomeningeal angiomas.[95]

• The advantages and disadvantages of MRI are summarized in Table 15.

Table 15.

Advantages and disadvantages of magnetic resonance imaging

Advantages	Disadvantages
No radiation exposure	Time-consuming
High resolution - submilimeter soft tissue delineation in vivo	Limited space inside machine. Many patients experience claustrophobia
3D imaging and planning possible	Expensive
Contrast agents less allergic as compared to those used in CT scans	Considerable space requirement
Multiplanar imaging	Interpretation of images requires considerable training
Functional imaging capability	Subject to motion artefacts
Excellent soft tissue contrast	Incompatible with many metallic devices

Fiber-optic endoscopy

Fiber-optic endoscopy is a minimally invasive medical imaging technique that utilizes a flexible tube with an embedded fiber-optic light source and camera to visualize internal structures, allowing for diagnostic and therapeutic procedures.[96]

Principle: Fiber-optic endoscopy involves using a flexible tube with an integrated fiber-optic light source and camera to visualize internal structures. The fiber-optic cables transmit light, illuminating the area of interest, while the camera captures real-time images. The flexibility of the endoscope allows it to navigate through body passages.[96]

This minimally invasive technique is widely applied for diagnostic and therapeutic purposes, enabling physicians to examine internal organs and perform procedures with reduced invasiveness and quicker recovery times.[96]

Fiber-optic endoscopy is crucial in hereditary angioedema (HAE) to assess laryngeal edema severity, monitor airway compromise, and guide interventions. It aids in prompt diagnosis, treatment planning, and evaluating response to therapies in individuals with this genetic disorder.[96] The procedure requires skillful manoeuvring, and patient discomfort or intolerance may impede the thorough examination of the laryngeal region.

Conclusion

The realm of medicine and science is continuously advancing, with new technologies emerging rapidly. Staying up-to-date with these developments is crucial not only for researchers but also for practicing clinicians. Dermoscopy is already well-known among dermatologists as a non-invasive imaging tool for aiding clinical diagnosis. In the coming years, many of the mentioned modalities are expected to become commonplace in clinical practice, potentially replacing older invasive techniques and reducing patient morbidity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.