Silicon-Based Avalanche Photodiodes in Medical Imaging

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This entry is adapted from the peer-reviewed paper 10.3390/nano13233078

Avalanche photodiodes have emerged as a promising technology with significant potential for various medical applications. Avalanche photodiodes offer distinct advantages over traditional photodetectors, including a higher responsivity, faster response times, and superior signal-to-noise ratios. These characteristics make avalanche photodiodes particularly suitable for medical-imaging modalities that require a high detection efficiency, excellent timing resolution, and enhanced spatial resolution.

photodetectors medical imaging positron emission tomography single-photon emission computed tomography time-of-flight positron emission tomography computed tomography fluorescence imaging bioluminescence imaging optical coherence tomography

1. Introduction

Medical imaging plays a crucial role in modern healthcare by enabling the non-invasive visualization and characterization of anatomical structures, physiological processes, and the detection of diseases ^[1]. Advancements in medical-imaging technologies have revolutionized the field of diagnostics and therapy. One key component of medical-imaging systems is the photodetector, which is responsible for capturing and converting optical signals into electrical signals for further analysis and image reconstruction. Photodetectors play a critical role in detecting and capturing optical signals in various medical-imaging modalities ^[2].

Traditionally, photomultiplier tubes (PMTs) and photodiodes have been the primary photodetectors used in medical imaging. PMTs, known for their high sensitivity and fast response times, have been extensively employed in applications such as positron emission tomography (PET) and gamma cameras. Photodiodes, on the other hand, offer a compact size, low power consumption, and excellent linearity, making them suitable for applications such as pulse oximetry and optical coherence tomography (OCT). However, both of these traditional photodetectors have limitations that hinder their performance and restrict their applications in certain areas of medical imaging.

Photodetectors may have a limited sensitivity to low levels of light, which can be a challenge in situations where the incident light is weak. Additionally, their dynamic range, or the ability to capture a broad range of light intensities, might be constrained. Photodetectors can introduce noise into the signal, affecting the overall quality of the image. High noise levels can decrease the signal-to-noise ratio, making it challenging to distinguish the desired signal from background noise. Achieving a high spatial resolution is another crucial task in medical imaging to visualize fine details. The physical size of photodetectors and their pixel density can limit the spatial resolution of the imaging system. Additionally, the physical size of the detectors may influence the design and portability of imaging devices. The response time of photodetectors can impact the speed at which images are acquired. In some medical applications, especially those involving moving organs or dynamic processes, a slow response time may result in motion artifacts. One other problem is that some photodetectors are sensitive to changes in temperature, and variations in temperature can affect their performance. Finally, in X-ray imaging, photodetectors can be exposed to ionizing radiation, which may lead to radiation damage over time. This can affect the long-term performance and reliability of the detectors.

To overcome these limitations, there has been a growing interest in the use of avalanche photodiodes (APDs) for medical purposes ^[3]. APDs are semiconductor-based devices that operate based on the avalanche multiplication effect, which enables the detection of weak optical signals with high sensitivity ^[4]. This unique characteristic of APDs makes them well-suited for various medical-imaging modalities, including PET, single-photon emission computed tomography (SPECT), fluorescence imaging, and OCT.

APDs offer several key advantages, including a high responsivity, fast response times, enhanced stability, and compact size. These features make APDs highly attractive for medical-imaging applications, where sensitive detection, rapid signal acquisition, and miniaturization are essential requirements ^[5]^[6]. Additionally, APDs have demonstrated a superior performance in terms of quantum efficiency, timing resolution, and spatial resolution, further enhancing their suitability for advanced medical-imaging techniques ^[7].

APDs can be integrated into detector modules, such as silicon photomultipliers (SiPMs). SiPMs are solid-state single-photon-sensitive devices based on an array of single-photon avalanche diodes (SPADs), implemented on a common silicon substrate. The dimensions of each individual SPAD can vary within the range of 10 to 100 μm, achieving a density of up to 10,000 per square millimeter. Each SPAD within a SiPM operates in Geiger mode (APD above breakdown) and is interconnected with others through a readout scheme. SiPMs are often considered analog devices due to the parallel reading of cells. SiPMs have a photodetection efficiency and gain comparable with PMTs. Moreover, SiPMs are not sensitive to external magnetic fields, have compact dimensions, and operate at lower voltages, enabling an extremely compact, light, and robust mechanical design.

2. Avalanche Photodiodes: Principles and Features

2.1. Operating Principles of Avalanche Photodiodes

APDs are advanced semiconductor devices that utilize the effect of the absorption of electromagnetic radiation to convert light into an electrical signal. APDs offer a high responsivity and fast response times, making them well-suited for various medical-imaging applications. APDs operate on the principle of avalanche multiplication, which allows for the detection of individual photons and conversion into measurable electrical signals.

2.2. Key Features of Avalanche Photodiodes

APDs offer several features that make them highly suitable for various imaging applications. These features contribute to their superior performance and make them a preferred choice over traditional photodetectors. The key features of APDs include:

High responsivity. APDs are capable of detecting low-level optical signals with high responsivity due to the avalanche multiplication effect. The internal gain mechanism amplifies the initial photo-generated carriers, allowing for the detection of weak signals that would otherwise be challenging to detect with traditional detectors;
Fast response time. APDs exhibit fast response times, typically in the order of picoseconds or nanoseconds. This fast response enables the detection and measurement of rapid optical events, making APDs suitable for applications that require precise timing information or fast real-time imaging capabilities to capture dynamic processes in medical visualization;
Wide spectral range. APDs are available in various semiconductor materials, such as silicon, germanium, and III-V compounds, allowing for a wide spectral range of operation. This versatility enables APDs to be utilized across different wavelengths, including visible, near-infrared, and even X-ray regions, depending on the choice of the semiconductor material;
Hybridization and integration with imaging systems. APDs can be integrated with other imaging components to enhance their capabilities and enable hybrid imaging systems. For instance, the combination of APDs with scintillator crystals enables the development of PET detectors, where APDs detect the scintillation light produced by the interaction of positrons with the scintillator material. The compatibility of APDs with various imaging modalities, including PET, SPECT, and time-resolved imaging, allows for the integration of APDs into versatile and multimodal imaging systems.

Compared to traditional photodetectors, such as photomultiplier tubes and photodiodes, APDs offer distinct advantages that make them particularly suitable for medical-imaging applications. The following points may be highlighted as the advantages of APDs over traditional photodetectors:

Higher responsivity. APDs provide a higher responsivity compared to traditional photodetectors due to the avalanche multiplication effect. This allows for the detection of weaker optical signals and enhances the overall signal detection efficiency in medical-imaging systems;
Compact size. APDs are typically smaller in size and have a more compact form factor compared to traditional photodetectors. This compactness enables their integration into miniaturized imaging devices and facilitates the development of portable and handheld medical-imaging systems;
Lower voltage operation. APDs operate at lower bias voltages compared to PMTs, making them more energy-efficient and reducing the power requirements of the imaging system. This advantage is particularly beneficial for battery-powered or mobile medical-imaging applications;
Enhanced stability. APDs exhibit better long-term stability and reduced aging effects compared to PMTs. This stability ensures a consistent performance over time, reducing the need for frequent recalibration and maintenance in imaging systems.

In summary, APDs operate on the principle of avalanche multiplication and offer key features such as a high responsivity, fast response times, wide spectral range, and compact size, making them a superior choice over traditional photodetectors in medical-imaging applications. Understanding the principles and operation of APDs is crucial for optimizing their performance, minimizing noise sources, improving timing resolution, and integrating them with other imaging components.

3. Applications of APDs in Medical Imaging

APDs have demonstrated significant potential in various medical-imaging applications. This section highlights the use of APDs in three key areas: positron emission tomography, optical imaging, and computed tomography. In all cases, an imaging installation consists of several main parts: source of radiation, positioning system, set of detectors, signal processing schemes, and visualization device (Figure 1).

Figure 1. Scheme of the typical biomedical-imaging tool.

3.1. Positron Emission Tomography (PET)

Positron emission tomography is a widely used imaging technique for studying physiological and biochemical processes, diagnosing and staging various diseases including cancer and neurological disorders. It is a non-invasive imaging modality that provides valuable information about organ function, metabolism, and molecular interactions ^[8]. PET imaging is based on the detection of positron-emitting radionuclides, which are short-lived radioactive isotopes. These isotopes are typically incorporated into biologically active molecules, such as glucose, water, or specific pharmaceuticals, to form radiotracers. The most commonly used radiotracer in PET is fluorodeoxyglucose (FDG), a glucose analog labeled with the positron-emitting isotope fluorine-18.

The imaging process begins with the administration of the radiotracer into the patient’s body, either by injection, inhalation, or ingestion, depending on the specific radiotracer and the organ or process being studied. Once inside the body, the radiotracer undergoes positron decay, wherein a positron (a positively charged particle) is emitted. Positrons have a short range in tissue, typically a few millimeters, before they encounter an electron. Upon encountering an electron, positrons undergo annihilation, resulting in the emission of two gamma photons traveling in approximately opposite directions. These photons are detected by a PET scanner, which consists of a ring of detectors surrounding the patient. The detectors in a PET scanner are typically scintillation crystals coupled to photodetectors, such as APDs or PMTs. When a gamma photon interacts with a scintillation crystal, it produces flashes of light, which are then converted into electrical signals by the photodetectors. The signals are processed and analyzed to reconstruct the distribution of radiotracer uptake in the body.

APDs have found extensive applications in PET due to their high quantum efficiency and excellent timing resolution at reasonable noise characteristics. In PET systems, APDs are commonly used as photodetectors in the scintillation crystals that detect the annihilation photons emitted by positron-emitting radiotracers. APDs offer enhanced responsivity and a high gain enabling the detection of low-energy photons and improving the overall image quality and quantitative accuracy. Additionally, APDs are particularly beneficial in time-of-flight PET, where the precise timing information of photon detection is crucial for reconstructing accurate images. Their fast response times enable precise time-of-flight measurements and better localization of the annihilation events, which can improve the spatial resolution and image reconstruction algorithms in PET. Silicon solid-state photomultipliers are now a mainstream solution for PET, enabling the creation of compact and highly sensitive PET systems ^[9]^[10]^[11].

3.2. Single-Photon Emission Computed Tomography (SPECT)

Single-photon emission computed tomography is a nuclear imaging technique used for functional imaging and molecular diagnostics. Like PET, SPECT relies on visualization of the distribution and function of radioactive tracers within the body ^[12]. It is commonly employed in clinical settings to diagnose and monitor a wide range of conditions, including cardiovascular diseases, neurological disorders, and cancer ^[13].

The SPECT imaging process begins with the injection of a radiopharmaceutical into the patient’s bloodstream. The radiopharmaceutical contains a gamma-emitting radioactive isotope, such as technetium-99m, which emits single photons during radioactive decay. The radiopharmaceutical is designed to selectively accumulate in specific organs or tissues of interest based on its biological properties. After the injection, the patient is positioned within a SPECT scanner, which consists of one or more gamma camera heads that rotate around the body. Each gamma camera head comprises a collimator, which is a lead or tungsten plate with small holes, and a scintillation crystal. The collimator allows only photons emitted in specific directions to pass through, while the scintillation crystal converts the gamma photons into visible light. As the gamma camera head rotates around the patient, it detects the emitted gamma photons that escape from the body and pass through the collimator. The scintillation crystal within the gamma camera head converts the detected photons into flashes of light. These light flashes are then detected by PMTs or solid-state photodetectors, which produce electrical signals proportional to the intensity of the light. The signals from the photodetectors are sent to a computer system, where sophisticated algorithms are employed to reconstruct the three-dimensional distribution of the radiotracer within the body. This reconstruction process generates cross-sectional slices, similar to those obtained in computed tomography (CT) scans, allowing for detailed visualization of the activity and function of the target organs or tissues.

One of the key advantages of SPECT is its ability to provide functional information, allowing the assessment of physiological processes in addition to anatomical structure. By using different radiopharmaceuticals with a specific affinity to various organs or processes, SPECT can assess blood flow, metabolism, receptor binding, and other functional parameters. SPECT offers several benefits in clinical practice. It is widely available, non-invasive, and relatively cost-effective compared to other imaging modalities. It provides valuable diagnostic information, helps in treatment planning, and aids in monitoring the response to therapy. SPECT is particularly useful in cardiology for assessing myocardial function, in neurology for evaluating cerebral blood flow and neuronal function, and in oncology for detecting and staging tumors.

However, SPECT also has some limitations. It has a lower spatial resolution compared to other imaging techniques like PET. The limited spatial resolution of SPECT can lead to reduced anatomical detail and decreased accuracy in localizing small lesions. Additionally, the imaging process in SPECT takes longer compared to PET, which can be a challenge for patients with limited mobility or discomfort.

Recently, advancements in SPECT technology have been made to address some of these limitations. Hybrid systems, such as SPECT/CT, combine the functional information from SPECT with the anatomical details provided by CT scans. Furthermore, the development of new collimator designs, advanced reconstruction algorithms, and higher-resolution detectors have contributed to enhanced image quality and spatial resolution in SPECT imaging.

APDs have been successfully employed in SPECT systems, providing enhanced responsivity, improved energy resolution, and reduced image blurring compared to conventional PMTs. The high gain of APDs enables the detection of weak gamma-ray signals, allowing for more accurate and detailed imaging. The integration of APDs into SPECT detectors has the potential to improve the image quality, increase the spatial resolution, and reduce the system size.

3.3. Time-of-Flight Positron Emission Tomography (TOF-PET)

Time-of-flight positron emission tomography is an advanced imaging technique that enhances the capabilities of conventional PET by incorporating time information into the imaging process. Unlike traditional PET, which relies solely on the detection of gamma photons and their spatial distribution, TOF-PET also utilizes the time-of-flight or time difference between the emission of a positron and the detection of the resulting annihilation photons to improve spatial resolution and signal-to-noise ratio (SNR) ^[14].

The principle behind TOF-PET is based on the fact that gamma photons travel at the speed of light. By accurately measuring the time it takes for the annihilation photons to reach the detectors after the emission of the positron, TOF-PET can provide additional information about the location of the annihilation event along the line of response (LOR).

The main advantage of TOF-PET is its ability to precisely determine the origin of annihilation photons, especially in cases where multiple annihilation events occur simultaneously along different LORs. By knowing the time difference between the photons’ emission and detection, the system can calculate the respective distances traveled by the photons and narrow down the possible locations of the annihilation event. This improved localization helps reduce image blurring and improves spatial resolution, leading to better lesion detectability and overall image quality.

Meanwhile, TOF-PET offers several other benefits over conventional PET imaging. First, it provides faster image acquisition times, as the temporal information allows for more efficient reconstruction algorithms. With shorter acquisition times, patients experience reduced scan durations, leading to increased patient comfort and improved workflow in clinical settings. Another advantage of TOF-PET is its superior signal-to-noise ratio. By accurately localizing the annihilation events, TOF-PET reduces the number of random coincidences, which occur when two unrelated photons are erroneously detected as simultaneous events. Moreover, TOF-PET enables lower administered radiotracer doses while maintaining image quality. With accurate timing information, TOF-PET compensates for the reduced statistics due to lower activity levels, making it suitable for pediatric and oncology applications where minimizing radiation exposure is important ^[15].

Despite its advantages, TOF-PET also presents some challenges. One significant challenge is the accurate timing resolution required for precise time measurements. The timing resolution determines the accuracy of the calculated time-of-flight information and is influenced by various factors, such as the detector technology, electronics, and the properties of the scintillation crystals used. Additionally, TOF-PET systems are more complex and expensive compared to conventional PET systems due to the need for fast and precise timing measurements. The detectors and electronics must be capable of high timing resolution to achieve the desired image quality. However, advancements in detector technology, such as the development of fast scintillators and dedicated time-resolving photodetectors like SiPMs, have facilitated the implementation of TOF-PET in clinical practice ^[16].

APDs with their fast response times and excellent timing resolution are well-suited for TOF-PET systems ^[17]. By accurately measuring the time-of-flight information, APDs enable precise localization of the annihilation events and reduce image artifacts. TOF-PET systems incorporating APDs have shown superior image quality and enhanced lesion detectability. The combination of APDs with TOF-PET has the potential to enhance the diagnostic accuracy and quantification capabilities of this imaging modality.

3.4. Computed Tomography (CT)

Computed tomography is a widely used imaging technique for anatomical visualization and disease diagnosis. CT uses X-rays and computer processing to create detailed cross-sectional images of the body. It provides a three-dimensional view of internal structures, allowing for the diagnosis, treatment planning, and monitoring of various medical conditions.

The CT imaging process involves the use of a specialized X-ray machine called a CT scanner. The patient lies on a motorized table that moves through the center of the scanner, while the X-ray tube and detector array rotate around them. The X-ray tube emits a narrow beam of X-rays that pass through the body and are detected by the detector array on the opposite side. The detectors measure the intensity of the X-rays that pass through the body, which varies depending on the density of the tissues encountered. The data from the detectors are then sent to a computer, which reconstructs the information into cross-sectional images or slices. These slices can be further processed to create three-dimensional images of the scanned area.

One of the key features of CT is its ability to differentiate tissues based on their X-ray attenuation properties. Different tissues, such as bone, muscle, and organs, have different densities and X-ray absorption characteristics. This enables the generation of high-resolution images that provide detailed anatomical information. Modern CT scanners can acquire images in rapid succession, allowing for the dynamic imaging of structures and the visualization of organ function over time. This capability is particularly useful in cardiac imaging, where CT angiography can assess blood flow and detect blockages in the coronary arteries. In some cases, contrast agents may be used to enhance the visibility of certain structures or abnormalities. These contrast agents, typically iodine-based, are administered orally, intravenously, or rectally, depending on the area being imaged. They help to highlight blood vessels, tumors, or other areas of interest, aiding in the diagnosis and characterization of various conditions.

CT imaging is used in a wide range of medical specialties, including radiology, oncology, neurology, orthopedics, and emergency medicine. It is valuable for diagnosing conditions such as fractures, tumors, infections, and vascular diseases. CT scans are also commonly used for surgical planning and image-guided interventions.

While CT imaging provides detailed anatomical information, it does involve exposure to ionizing radiation. However, modern CT scanners are equipped with dose-reduction techniques to minimize radiation exposure while maintaining image quality. It is important for healthcare professionals to weigh the benefits of CT imaging against the potential risks and ensure that the procedure is justified for each patient.

APDs have emerged as a promising alternative to traditional PMTs in CT systems, offering advantages such as a higher spatial resolution, compact size, and lower power consumption. The use of APDs in CT detectors enables improved image quality, faster acquisition times, and a reduced radiation dose to the patient. SiPMs, a type of APD, have gained attention in CT due to their high photon detection efficiency, excellent timing resolution, and immunity to magnetic fields ^[7]. SiPM-based CT detectors have shown promise in applications such as cardiovascular imaging and CT angiography. APDs can be integrated into hybrid CT systems, such as PET/CT and SPECT/CT, enabling the combination of anatomical and functional information for more comprehensive diagnostics ^[18].

3.5. Fluorescence Imaging

In addition to tomography methods, APDs have been employed in optical imaging techniques, such as fluorescence molecular imaging and bioluminescence imaging. These techniques rely on the detection of light emitted from fluorescent probes or bioluminescent reporters to visualize molecular and cellular processes ^[19]^[20].

Fluorescence imaging is a non-invasive medical-imaging technique that utilizes the emission of fluorescent light from molecules or probes to visualize specific biological processes, structures, or targets within living organisms. It has gained significant popularity in biomedical research and clinical applications due to its high sensitivity, real-time imaging capabilities, and ability to provide molecular-level information.

The fluorescence imaging process involves the use of fluorescent probes or dyes that are designed to bind to specific molecules or structures of interest. These probes contain a fluorophore, a molecule that can absorb light at a specific wavelength and emit light at a longer wavelength upon excitation. The excitation light, typically provided by a light source such as a laser or LED, is directed onto the tissue or sample being imaged. When the excitation light interacts with the fluorescent probe, the fluorophore molecules become excited and subsequently emit fluorescent light at a longer wavelength. This emitted light is then captured by a detector, such as a camera or a specialized imaging system, which converts the light signals into a visual image or quantitative data ^[21].

One of the key advantages of fluorescence imaging is its high sensitivity and specificity ^[22]. By using fluorescent probes that selectively bind to specific molecules or targets, researchers and clinicians can visualize and track the distribution, localization, and activity of these targets within biological samples or living organisms. This allows for the study of various cellular processes, such as gene expression, protein interactions, enzyme activity, and molecular signaling pathways.

Fluorescence imaging can also be combined with other imaging modalities to provide complementary information. For example, combining fluorescence imaging with anatomical imaging techniques like CT or MRI allows for the correlation of molecular information with structural context, enhancing the understanding and interpretation of biological processes.

Fluorescence imaging has found widespread applications in various fields, including cancer research, neurobiology, immunology, and drug discovery. It has contributed to the understanding of disease mechanisms, the development of new therapeutic approaches, and the evaluation of treatment responses. Moreover, fluorescence imaging has the potential for clinical translation, with applications in surgical guidance, tumor detection, and the monitoring of therapeutic interventions.

APDs have been employed in fluorescence imaging systems to enhance sensitivity and improve signal detection ^[23]^[24]. The high gain of APDs enables the detection of weak fluorescence signals, allowing for the visualization of subtle molecular events. APDs can be utilized in various fluorescence imaging modalities, including fluorescence microscopy, fluorescence lifetime imaging microscopy (FLIM), and fluorescence molecular tomography (FMT). For all these techniques, APDs offer advantages in terms of their high responsivity and wide dynamic range, enabling the detection of weak light signals and facilitating quantitative measurements.

3.6. Bioluminescence Imaging

Bioluminescence imaging is a non-invasive imaging technique that utilizes the light emitted by bioluminescent organisms or genetically modified cells to visualize biological processes in living organisms. It relies on the production of light by naturally occurring or engineered bioluminescent molecules, such as luciferase enzymes, which emit photons upon a specific biochemical reaction ^[25]. The process of bioluminescence imaging involves introducing a bioluminescent probe or gene into the target cells or organisms of interest. This probe or gene encodes for a bioluminescent protein which can produce light through a series of enzymatic reactions.

To initiate the bioluminescent reaction, a substrate molecule, such as luciferin, is administered to the subject. When the substrate interacts with the bioluminescent protein, it undergoes an enzymatic reaction that results in the emission of light. The emitted photons are then detected by a highly sensitive camera or imaging system, allowing for the visualization and quantification of the bioluminescent signal.

One of the main advantages of bioluminescence imaging is its high sensitivity ^[26]. The emitted bioluminescent signal is relatively weak, but it can be detected with very low background noise due to the absence of endogenous bioluminescence in mammalian tissues. This enables the detection of even small numbers of bioluminescent cells or organisms in vivo. Bioluminescence imaging is commonly used in preclinical research to study various biological processes and phenomena. It has been extensively employed in fields such as cancer research, immunology, neurobiology, and infectious disease studies. By introducing bioluminescent reporter genes into specific cell types or organisms, researchers can track and monitor their behavior, migration, proliferation, and response to stimuli or treatments over time ^[27].

Another significant advantage of bioluminescence imaging is its ability to provide longitudinal and real-time information. Since the emitted light is directly proportional to the number of bioluminescent cells or the activity of the bioluminescent reporter, changes in signal intensity can be correlated with the underlying biological processes. This allows for the assessment of disease progression, therapeutic responses, and the evaluation of novel therapies in living subjects over time.

However, it is important to note that bioluminescence imaging has limitations. The emitted light is subject to scattering and absorption within tissues, which can limit the spatial resolution and depth penetration of the imaging signal. Additionally, the emitted photons can only provide information about the location and intensity of the bioluminescent signal, without revealing detailed anatomical structures or functional parameters. To overcome some of these limitations, bioluminescence imaging is often combined with other imaging modalities, such as CT or MRI. This allows for the integration of anatomical information with the bioluminescent signal, providing a more comprehensive view of the target site and facilitating data interpretation ^[28].

APDs offer a high responsivity and the detection of low signals, making them well-suited for bioluminescence imaging applications. By incorporating APDs into bioluminescence imaging systems, researchers can achieve improved signal detection, higher spatial resolution, and enhanced quantification of bioluminescent signals ^[29]. Their compact size and compatibility with small-animal imaging systems make APDs suitable for preclinical research and drug development studies.

3.7. Optical Coherence Tomography (OCT)

Furthermore, APDs can be integrated with advanced imaging modalities like optical coherence tomography to enhance imaging capabilities. Optical coherence tomography is a non-invasive imaging technique that provides cellular level cross-sectional imaging of biological tissues in real time. It utilizes low-coherence interferometry to capture and analyze the backscattered or back-reflected light from biological tissues ^[30].

The principle of OCT is analogous to ultrasound imaging, but instead of sound waves, it employs near-infrared light. The system consists of a broadband light source, typically a superluminescent diode or a femtosecond laser, which emits light with a broad spectrum of wavelengths. The light is split into two paths: the sample arm and the reference arm. In the sample arm, the light is directed towards the tissue being imaged. A scanning mechanism, such as a galvanometer mirror, is used to steer the light beam across the tissue surface or within the tissue. As the light interacts with the tissue, a portion of it is backscattered or back-reflected due to variations in the refractive index and scattering properties of different tissue structures. Simultaneously, in the reference arm, the light travels through a reference path of known length. This path usually consists of a mirror or a reference reflector. The light from the reference arm is combined with the backscattered light from the sample arm using a beamsplitter. The combined light from both arms is then directed to an interferometer, where interference occurs between the reference light and the backscattered light from the sample. The interference pattern carries information about the depth and intensity of the backscattered light at different locations within the tissue.

To obtain cross-sectional images, the interference pattern is detected using a photodetector and processed by an OCT system. The system measures the time delay or phase difference between the reference and sample arms at each depth position. By scanning the light beam across the tissue or by moving the sample, a series of depth profiles are acquired. By combining multiple depth profiles obtained at adjacent positions, a two-dimensional cross-sectional image is generated. These two-dimensional images can be further combined to form three-dimensional volumetric images of the tissue ^[31].

OCT provides high-resolution images with a micrometer-scale axial and lateral resolution, allowing for the detailed visualization of tissue structures and cellular morphology. It has a wide range of applications in ophthalmology, dermatology, cardiology, gastroenterology, and other medical fields. One of the significant advantages of OCT is its non-invasive nature, which enables the real-time imaging of biological tissues without the need for tissue excision or contrast agents. It allows clinicians and researchers to observe tissue morphology, identify abnormalities, and monitor disease progression or treatment response. Moreover, OCT can be enhanced with various imaging modes to extract additional information.

APDs have been employed in OCT systems to enhance detection sensitivity and improve image quality ^[32]. The high gain characteristics of APDs enable the detection of weak optical signals, allowing for deeper tissue penetration and higher imaging depths ^[33]. By utilizing APDs in OCT, one can achieve a higher resolution, faster imaging speeds, and improved visualization of structural and functional information in biological tissues ^[34]. High-resolution imaging and improved depth penetration for applications such as ophthalmology, cardiovascular imaging, and cancer detection have already been obtained.

Overall, APDs have demonstrated their potential in various medical-imaging applications, including PET, optical imaging, and CT. Their unique characteristics such as a high responsivity and fast timing response contribute to enhanced image quality, improved diagnostic accuracy, and reduced radiation exposure. Continued advancements in APD technology and their integration into imaging systems hold great promise for further advancements in medical imaging.

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Kirill A. Lozovoy

Rahaf M. H. Douhan

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Kristina I. Khomyakova

Olzhas I. Kukenov

Arseniy S. Sokolov

Nataliya Yu. Akimenko

Andrey P. Kokhanenko

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Update Date: 13 Dec 2023

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