Monitoring Of Therapeutic Response Research Articles

Targeted Sequencing of Circulating Tumor DNA to Monitor Genetic Variants and Therapeutic Response in Metastatic Colorectal Cancer.

Substantial improvements have been made in the management of metastatic colorectal cancer (mCRC) in the last two decades, but disease monitoring remains underdeveloped. Circulating tumor DNA (ctDNA) is a promising prognostic and predictive biomarker; however, ctDNA as a marker for mCRC patients is not well established, and there is still no consensus about how to utilize it most cost-effectively. In this study, we aim to investigate plasma ctDNA levels as a biomarker for therapeutic response of mCRC patients. We performed next-generation sequencing (NGS) by using a 12-gene panel to identify genetic variants in 136 tumor tissue and ctDNA samples from 32 mCRC patients. Genetic variants were detected in approximately 70% of samples, and there was a high concordance (85%) between tumor tissue and plasma ctDNA. We observed ctDNA changes in 18 follow-up patients, including the emergence of new variants. Changes in ctDNA levels significantly correlated with tumor shrinkage (P = 0.041), and patients with a ctDNA decrease >80% after treatment had a longer progression-free survival compared with patients with a ctDNA decrease of <80% (HR, 0.22; P = 0.015). The objective response rate among patients with a ctDNA decrease of >80% was better than those with a ctDNA decrease <80% (OR, 0.026; P = 0.007). In conclusion, this study demonstrates that monitoring of genetic ctDNA variants can serve as a valuable biomarker for therapeutic efficacy in mCRC patients, and that using a moderate-sized 12-gene NGS panel may be suitable for such clinical monitoring. Mol Cancer Ther; 17(10); 2238-47. ©2018 AACR.

Application of Photoacoustic Methods and Confocal Microscopy for Monitoring of Therapeutic Response in Plaque Psoriasis

Psoriasis is prone to relapses and requires long-term therapy that may induce a range of adverse effects; therefore, an efficient and early detection of relapses is desirable. In this study, photoacoustic imaging and confocal laser scanning microscopic (CLSM) methods were investigated for their suitability in psoriasis follow-up examinations. Using a high-resolution photoacoustic system, the vascular structures of 11 psoriatic patients and 6 healthy volunteers were investigated. No differences were detected with respect to the average vessel diameter and vasculature per unit volume in the tissue of healthy volunteers and non-lesional and lesional skin areas of psoriatic patients. By means of CLSM, the diameters of the dermal papillae of 6 volunteers and 6 psoriatic patients were determined. The diameters of the dermal papillae of the healthy volunteers (0.074 ± 0.006 mm) revealed no significant difference when compared to non-lesional skin areas of psoriatic patients (0.079 ± 0.005 mm). The results obtained for the lesions in psoriatic patients showed a significant difference (Wilcoxon test, p = 0.028) between the diameters of the dermal papillae of the lesional skin areas (0.114 ± 0.012 mm) and the non-lesional skin areas (0.079 ± 0.005 mm). Thus, CLSM can be applied for monitoring psoriasis follow-up examinations.

Abstract B068: Methionine aminopeptidase II (MetAP2) activated in situ self-assembly of small-molecule probes for imaging prostate cancer

Abstract Prostate cancer is the most common noncutaneous malignancy among men in the United States and a leading cause of cancer death worldwide. The major clinical challenges in prostate cancer diagnosis include accurate staging, localizing tumors within the prostate, and developing imaging prognostic biomarkers. PET is routinely used in the clinical management of many cancers dues to its high sensitivity (10-15 M), spatial resolution (2-4 mm3), rapid whole-body scan times (&amp;lt;20 min), noninvasiveness, and its ability to provide both anatomic and molecular information when combined with computed tomography (PET/CT). Several PET tracers (e.g., 18F-FDG, 18F-NaF, 11C-choline, 11C-acetate, 18F-fluciclovine, etc.) have been studied for early stage prostate cancer, bone metastases, and recurrent disease; nevertheless, all of these tracers rely on cell uptake and their applications are often limited by the low metabolic activity and a low growth rate of prostate cancer. In this project, we aim to develop a novel enzymatic activity-based PET tracer for in vivo imaging of prostate cancer by targeting methionine aminopeptidase II (MetAP2), a cytosolic metalloprotease that catalyzes the cotranslational removal of the N-terminus initiator methionine residue from nascent proteins. We hypothesize that MetAP2 can serve as a novel diagnostic biomarker of prostate cancer. A MetAP2 activatable molecular imaging probe that self-aggregates in situ can be utilized to image and define this disease. To test our hypothesis, we first measured the expression level of MetAP2 in primary benign human prostate epithelial cells (BS403) and prostate tumor cell lines by Western blot. BS403 cells express significantly lower levels of MetAP2 than PC3 (by 4-fold), DU145 (3-fold), and 22Rv1 (3-fold). The expression of MetAP2 in DU145 tumor xenografts is 12-fold higher and for 22Rv1 14-fold higher, compared to BS403 cells. Immunohistologic analysis of tissues derived from DU145 and 22Rv1 xenografts confirms strong staining of MetAP2. We performed immunohistochemistry on a prostate cancer tissue microarray containing 225 independent patient samples represented in quadruplicate. Positive staining for MetAP2 was found in nearly all of the cancer samples. Encouraged by these data, we designed and synthesized a nonradioactive MetAP2 sensitive nano-aggregation probe called M-SNAP. Incubation of M-SNAP with recombinant MetAP2 enzyme confirmed the formation of the cyclized and aggregated product M-SNAP-cycl by HPLC, TEM (transmission electron microscopy), and DLS (dynamic light scattering). Treatment of PC3 and DU145 cells with or without M-SNAP and the MetAP2 specific inhibitor TNP470 demonstrated MetAP2 dependent intracellular probe aggregation/signal retention using post fluorescent labeling of the cyclized and aggregated products. In future work, we will prepare and study an MetAP2 activatable radioisotope-labeled probe in vitro for sensing and imaging and will evaluate the PET probe in different human prostate xenograft models. MetAP2 sensing probes could provide a highly sensitive and noninvasive PET imaging approach for prostate cancer detection that could be useful in prostate cancer detection, staging, and monitoring of therapeutic response. Citation Format: Jinghang Xie, Meghan Rice, Yunfeng Cheng, Guosheng Song, Christian Kunder, James D. Brooks, Tanya Stoyanova, Jianghong Rao. Methionine aminopeptidase II (MetAP2) activated in situ self-assembly of small-molecule probes for imaging prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B068.

Polysiloxanes in Theranostics and Drug Delivery: A Review.

One of the historical problems of medicine is that often, diagnosis and therapy do not interface, at best. Moreover, especially in some areas, such as oncology, the stress for the organism during the two phases (diagnosis and therapy) can become excessive, and be fatal to the success of the treatment. The extraordinary progress of nanotechnology in the last 25 years has offered the opportunity to build a nanoplatform able to ferry drugs, and loads onto them both imaging and therapeutic functions, thus creating nanosystems capable of diagnosis, drug delivery, and monitoring of therapeutic response. The purpose of this unusual, and up to recent times, unimaginable, marriage between diagnosis and therapeutics is the reaching of protocols more specific to individuals. The dual use of particles/device lead to a personalized medicine. Due to their biocompatibility, versatility, physical and chemical resistance, and ability to be functionalized, silica nanoparticles and polysiloxanes are the heart and the shield of this nanoplatform, respectively. In this short review, I analyze the applications of these silicon-based materials in the field of controlled drug delivery.

Role of Computed Tomography Perfusion Compared to Computed Tomography Triphasic Study in Assessment of Hepatic Focal Lesions

Purpose of this study is: to evaluate the role of computed tomography perfusion and computed tomography triphasic in assessment of hepatic focal lesions. Methods: The study included 43 patients (between 30 to 60 years old) referred from radiodiagnosis department. Each patient included in the study was subjected to full history taking and availability of the previous studies. Results: The study showed that CT perfusion revealed more accurate results than CT triphasic. Conclusion: The current application of CT perfusion to patient with hepatic focal lesions showed that it enhanced our understanding of the disease diagnosis staging, prognostic evaluation and monitoring therapeutic response.

Liquid Biopsy in Oral Cancer.

Oral cancer is one of the most prevalent forms of cancer worldwide. Carcinogenesis is a complex process, in which heterogeneity plays an important role in the development and progression of the disease. This review provides an overview of the current biological and clinical significance of circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), and exosomes for diagnosis and prognosis of oral cancer. We highlight the importance of liquid biopsy—using blood and saliva—which represents a potential alternative to solid biopsy for diagnosis and prognosis. Moreover, liquid biomarkers allow for the real-time monitoring of tumour evolution and therapeutic responses, initiating the era of personalized medicine. However, in oral cancer, the impact of liquid biopsies in clinical settings is still limited, requiring further studies to discover the best scenario for its clinical use.

Cancer in the crosshairs: targeting cancer metabolism with hyperpolarized carbon-13 MRI technology.

Magnetic resonance (MR)-based hyperpolarized (HP) 13 C metabolic imaging is under active pursuit as a new clinical diagnostic method for cancer detection, grading, and monitoring of therapeutic response. Following the tremendous success of metabolic imaging by positron emission tomography, which already plays major roles in clinical oncology, the added value of HP 13 C MRI is emerging. Aberrant glycolysis and central carbon metabolism is a hallmark of many forms of cancer. The chemical transformations associated with these pathways produce metabolites ranging in general from three to six carbons, and are dependent on the redox state and energy charge of the tissue. The significant changes in chemistry associated with flux through these pathways imply that HP imaging can take advantage of the underlying chemical shift information encoded into an MR experiment to produce images of the injected substrate as well as its metabolites. However, imaging of HP metabolites poses unique constraints on pulse sequence design related to detection of X-nuclei, decay of the HP magnetization due to T1 , and the consumption of HP signal by the inspection pulses. Advancements in the field continue to depend critically on customization of MRI systems and pulse sequences for optimized detection of HP 13 C signals, focused largely on extracting the maximum amount of information during the short lifetime of the HP magnetization. From a clinical perspective, the success of HP 13 C MRI of cancer will largely depend upon the utility of HP pyruvate for the detection of lactate pools associated with the Warburg effect, though several other agents are also under investigation, with novel agents continually being formulated. In this review, the salient aspects of HP 13 C imaging will be highlighted, with an emphasis on both technological challenges and the biochemical aspects of HP experimental design.

Intravital Imaging to Monitor Therapeutic Response in Moving Hypoxic Regions Resistant to PI3K Pathway Targeting in Pancreatic Cancer

SummaryApplication of advanced intravital imaging facilitates dynamic monitoring of pathway activity upon therapeutic inhibition. Here, we assess resistance to therapeutic inhibition of the PI3K pathway within the hypoxic microenvironment of pancreatic ductal adenocarcinoma (PDAC) and identify a phenomenon whereby pronounced hypoxia-induced resistance is observed for three clinically relevant inhibitors. To address this clinical problem, we have mapped tumor hypoxia by both immunofluorescence and phosphorescence lifetime imaging of oxygen-sensitive nanoparticles and demonstrate that these hypoxic regions move transiently around the tumor. To overlay this microenvironmental information with drug response, we applied a FRET biosensor for Akt activity, which is a key effector of the PI3K pathway. Performing dual intravital imaging of drug response in different tumor compartments, we demonstrate an improved drug response to a combination therapy using the dual mTORC1/2 inhibitor AZD2014 with the hypoxia-activated pro-drug TH-302.

Therapeutic response monitoring using digital PCR for patient-specific circulating tumor DNA identified by an esophageal squamous cell carcinoma-specific sequencing panel.

e24089Background: Esophageal squamous cell carcinoma (ESCC) is belligerent cancer with a poor prognosis. At present, no specific ESCC biomarkers for therapeutic monitoring have been established. Th...

Biomarkers in Type 2 Diabetes

Biomarkers are measurable substances in an organism indicative of disease such as Type 2 diabetes. Biomarkers are utilized to obtain necessary information about a certain disease such as Type 2 diabetes. Type 2 diabetes is estimated to be the 7th leading cause of mortality by 2030, according to the World Health Organization. Comprehending the number of biomarkers that affect Type 2 diabetes will be the focus of this review. Obtaining different classes of biomarkers related to Type 2 diabetes could enable researchers to identify and characterize levels of Type 2 diabetes inception. Thus, they represent a logical way to improve diagnosis, track progression and activity, guide molecularly targeted therapy and monitor therapeutic response to Type 2 diabetes. Furthermore, great effort has been put into the identification of novel biomarkers. A comprehensive overview associated with Type 2 diabetes will be presented.

Localized Single Transcript Detection of Eml4‐Alk in NSCLC using Co‐localization Quantum Dot Fluorescent In Situ Hybridization (CoQFISH)

Lung cancer remains one of the most common forms of cancer worldwide with more than 80% being non-small cell lung cancer (NSCLC). Two primary clinical tests are used to identify NSCLC subtypes through the detection of EGFR mutation and oncogenic gene fusions such as EML4-ALK. Since the discovery of EML4-ALK, there has been a multitude of targeted therapies such as ALK inhibitors alectinib, ceritinib, and crizotinib, which has shown great success in treatment. However, the methods for clinical detection of gene fusions remains constant through either RT-PCR or Break Apart FISH. By observing co-localization of signal in oligonucleotide conjugated quantum dots, we designed a novel co-localization based quantum dot fluorescent in situ hybridization (CoQFISH) technology capable of detecting sensitively and specifically single localized fusion transcripts using as little as two oligonucleotide probes in cell lines and tissue. We found that CoQFISH can detect EML4-ALK transcripts in a positive control NSCLC cell line H2228 using the co-localization of Eml4 and Alk targeted probe sets, which was verified through qPCR and targeted RNA-seq. Furthermore, we found that CoQFISH can positively identify EML4-ALK transcripts in human NSCLC tissue biopsies at a sensitivity that is higher than qPCR and RNA sequencing and offer information on the spatial location of each transcript. Looking further, quantum dot probes in CoQFISH are uniquely suited for resolving smaller areas on transcripts for identification of targets such as gene isoform transcripts. This novel technology would not only aid in research on understanding fusion genes and small RNA transcripts, but more importantly allow more sensitive diagnostics of potential cancer targets meaning earlier detection and better therapeutic response monitoring. Detection of CoQFISH probes targeting GAPDH. Positive signal was detected in human lung tissue for the positive control containing GAPDH (left). Human tissue was treated with RNAse treatment in the negative control (right) and showed no detected signal. CoQFISH detects Eml4-Alk fusion transcripts. Differential interference contrast (DIC) shows human non-small cell lung cancer tissue structure on the right. Co-localized signal from Eml4 (middle) and Alk (right) is indicated with the corresponding arrows. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

How to use… a blood film

The diagnostic relevance of the blood film cannot be underestimated in the assessment of children with suspected primary or secondary haematological conditions. The blood film not only serves as a...

Ultrasonographic images of the hand in a case with early eosinophilic fasciitis

Eosinophilic fasciitis (EF), a rare rheumatic disease, usually affects the limbs symmetrically and generally spares the hands and feet. Cases of unilateral hand involvement are rarely reported. Here, we report such a rare case. Ultrasonography demonstrated thickening of the overlying skin and subcutaneous tissue, peripheral deep fascia, myositis of lumbrical muscles and adductor pollicis muscle, and edema surrounding flexor digitorum tendons. It reminds us that EF should be considered in the differential diagnosis of unilateral painful hand swelling despite being uncommon. Ultrasonography can be used to aid the diagnosis and monitor therapeutic response in patients with EF.

Nerve Ultrasound Predicts Treatment Response in Chronic Inflammatory Demyelinating Polyradiculoneuropathy-a Prospective Follow-Up.

As reliable biomarkers of disease activity are lacking, monitoring of therapeutic response in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) remains a challenge. We sought to determine whether nerve ultrasound and electrophysiology scoring could close this gap. In CIDP patients (fulfilling EFNS/PNS criteria), we performed high-resolution nerve ultrasound to determine ultrasound pattern sum scores (UPSS) and predominant echotexture nerve conduction study scores (NCSS) as well as Medical Research Council sum scores(MRCSS) and inflammatory neuropathy cause and treatment disability scores(INCAT) at baseline and after 12months of standard treatment. We retrospectively correlated ultrasound morphology with nerve histology when available. 72/80 CIDP patients featured multifocal nerve enlargement, and 35/80 were therapy-naïve. At baseline, clinical scores correlated with NCSS (r2 = 0.397 and r2 = 0.443, p < 0.01), but not or hardly with UPSS (Medical Research Council sum scoresMRCSS r2 = 0.013, p = 0.332; inflammatory neuropathy cause and treatment disability scoresINCAT r2 = 0.053, p = 0.048). Longitudinal changes in clinical scores, however, correlated significantly with changes in both UPSS and NCSS (r2 = 0.272-0.414, p < 0.0001). Combining nerve/fascicle size with echointensity and histology at baseline, we noted 3 distinct classes: 1) hypoechoic enlargement, reflecting active inflammation and onion bulbs; 2) nerve enlargement with additional hyperechogenic fascicles/perifascicular tissue in > 50% of measured segments, possibly reflecting axonal degeneration; and 3) almost no enlargement, reflecting "burned-out" or "cured" disease without active inflammation. Clinical improvement after 12months was best in patients with pattern 1 (up to 75% vs up to 43% in pattern 2/3, Fisher's exact test p < 0.05). Nerve ultrasound has additional value not only for diagnosis, but also for classification of disease state and may predict treatment response.

Nuclear Medicine Applications in Pediatric Musculoskeletal Diseases: The Added Value of Hybrid Imaging.

The introduction of diphosphonates in the 1970s revolutionized not only nuclear medicine but musculoskeletal imaging as well, providing functional assessment of entities such as osteomyelitis, trauma, and osseous metastatic disease. Although rarely the first-line imaging modality used today, nuclear medicine procedures continue to play a pivotal role in the evaluation of musculoskeletal diseases in children, providing whole-body assessment of disease involvement. More recently, the introduction of technologies such as single-photon emission computed tomography/computed tomography (SPECT/CT), as well as newer positron-emitting tracers such as 18fluorine-fluorodeoxyglucose and sodium 18F-fluorine, particularly when combined with CT (positron emission tomography/CT), have injected new life into the older established techniques and expanded the application of nuclear medicine imaging into new arenas. This article discusses the utility of standard nuclear medicine procedures as they apply to children with musculoskeletal disorders, focusing on the added value of and indications for SPECT/CT. Subsequently, we discuss the expanding role of positron-emitting agents in infection, trauma, and for the diagnosis, staging, and therapeutic response monitoring of children with malignant bone and soft tissue tumors. Differences between disease processes encountered in children as compared with adults are discussed; developmental variants that can, but should not, be confused with disease are illustrated. The need for pediatric-specific protocols is addressed.

Applying host disease status biomarkers to therapeutic response monitoring in invasive aspergillosis patients.

One critical factor impeding successful management of invasive aspergillosis (IA) is the lack of reliable biomarkers to assess therapeutic response. We hypothesized that changes in certain host biomarkers reflect the nature of infection status and disease progression. Upon primary IA diagnosis, these disease status biomarkers can be monitored to track response to antifungal therapy and provide early markers that prognosticate likelihood of response. Herein, we analyzed serum levels of three prominent host disease status biomarkers C-reactive protein (CRP), haptoglobin (Hp), and annexin A1 (ANXA1) in IA patients during antifungal therapy. A total of 81 serial serum samples were collected at five or six different time points relative to IA diagnosis from 15 probable IA patients (10 acute leukemia [AL] and five hematopoietic stem cell transplantation [HSCT]). Of note, different biomarker profiles were observed in AL and HSCT patients, as not only levels of markers were significantly lower in HSCT patients but also more prominent interconnections among markers were observed in AL patients. Using a composite evaluation, patients were categorized as responders, nonresponders, and stable cases at last specimen. For AL responders, typical biomarker profiles were high initially but rapidly decreased for CRP and Hp post antifungal therapy, while low initial ANXA1 values were restored to normal levels after treatment. In contrast, CRP and Hp were persistently elevated whilst ANXA1 remained low throughout therapy in AL non-responders. As a pilot proof-of-concept study, our work demonstrates the great potential of using host biomarkers to monitor early therapeutic response in leukemia patients.

Therapeutic response monitoring in canine babesiosis – case study

The present paper constitutes an example for the clinician regarding babesiosis diagnostic workflow, parasitic load monitoring in correlation with specific treatment and therapeutic efficiency for disease, as well as infection removal. The results obtained, as standalone or in correlation with the symptomatology and paraclinical routine tests, are able to generate a high level of information, therefore allowing the clinician to have a correct approach for the two main objectives in disease management – patient’s recovery and removal of the specific cause.

An exosomal- and interfacial-biosensing based strategy for remote monitoring of aberrantly phosphorylated proteins in lung cancer cells.

It is a well-known phenomenon that cancer cells release key biological information such as DNA, RNA or proteins into body fluids (e.g., blood, urine or saliva). The analysis of these molecules-often encapsulated within nanovesicules called exosomes-is highly attractive, because it could replace current surgical biopsies, which are painful, costly and potentially risky for patients. For example, current strategies in lung cancer diagnosis involve genetic analyses from tumour tissues to detect the presence of underlying DNA mutations, known to alter the phosphorylation status and function of proteins. This information is used to direct therapy, as aberrantly phosphorylated proteins are the main targets of current drugs such as Tyrosine Kinase Inhibitors (TKIs). An alternative and less invasive strategy would be the remote analysis of these phospho-proteins by isolating them from cancer-derived exosomes. This would allow evaluating not only their phosphorylation status at diagnosis, but also the timely restoration of protein phosphorylation levels during therapy with TKIs. Yet, this proteomic approach remains vastly unexplored. Herein, we demonstrate that key lung cancer phosphoproteins, such as EGFR and ERK, are expressed in lung cancer exosomes and we outline a new exosomal proteomic-based approach for their fast and convenient detection. This approach, which could complement current genetic analysis for lung cancer detection, easily detects the phosphorylation status of lung cancer exosomal proteins within minutes after their extraction, bringing hope of circumventing the need for tissue biopsy and costly and cumbersome DNA sequencing techniques. It exploits the fact that phosphorylation induces protein conformational changes, which in turn alter protein's ability to effectively interact with bare gold surfaces. This leads to phosphorylated and non-phosphorylated protein isoforms displaying different gold-adsorption profiles. Using single-use and inexpensive, gold (Au) screen-printed electrodes (SPEs), we demonstrate the successful detection of aberrantly phosphorylated EGFR and ERK protein isoforms derived from lung cancer cell exosomes with a sensitivity down to 15 ng μL-1 in samples with up to 90% excess of their non-phosphorylated (wild-type) forms. We further show the applicability of this strategy for monitoring the action of Tyrosine Kinase Inhibitors over time. We believe that this non-invasive technique will open up new avenues for facilitating cancer diagnosis and time-point monitoring of therapeutic responses.

Photonic monitoring of treatment during infection and sepsis: development of new detection strategies and potential clinical applications.

Despite the strong decline in the infection-associated mortality since the development of the first antibiotics, infectious diseases are still a major cause of death in the world. With the rising number of antibiotic-resistant pathogens, the incidence of deaths caused by infections may increase strongly in the future. Survival rates in sepsis, which occurs when body response to infections becomes uncontrolled, are still very poor if an adequate therapy is not initiated immediately. Therefore, approaches to monitor the treatment efficacy are crucially needed to adapt therapeutic strategies according to the patient's response. An increasing number of photonic technologies are being considered for diagnostic purpose and monitoring of therapeutic response; however many of these strategies have not been introduced into clinical routine, yet. Here, we review photonic strategies to monitor response to treatment in patients with infectious disease, sepsis, and septic shock. We also include some selected approaches for the development of new drugs in animal models as well as new monitoring strategies which might be applicable to evaluate treatment response in humans in the future. Figure Label-free probing of blood properties using photonics.

Guest Editorial Low-Dose CT: What Has Been Done, and What Challenges Remain?

The introduction of computed tomography (CT) in 1972 was among the most significant development in medical imaging since the discovery of X-rays in 1895. In addition, the innovation of computationally reconstructing tomographic images from projection data significantly influenced the development of other medical imaging modalities, such as magnetic resonance imaging and single photon and positron emission tomography. With the advent of helical and multi-detector-row CT (MDCT) scanners in the 1990s and 2000s along with innovations in cone-beam CT (CBCT) in many forms, CT gained unmatched speed and adaptability for volumetric imaging, leading to widespread use for diagnostic imaging, emergency examination, image-guided interventions, treatment planning, and monitoring of therapeutic response.