Next-level precision medicine: why the theragnostic approach is the future.

Theragnostics represents one of the most innovative fields of precision medicine with a huge potential in the field of oncology in the next years. The use of a pair of selective radiopharmaceuticals for cellular receptors, used for diagnostic and therapeutic purposes (PRRT), finds applications in the Neuroendocrine tumors and metastatic Castration-Resistant prostate cancer (mCRPC) thanks, respectively, to somatostatin receptor agonists and PSMA-based peptides. Further evolutions of theragnostics will be possible to the radioimmunoconjugates used both in the diagnostic (Immuno-PET) and in the therapeutic fields (radioimmunotherapy). It is evident that in the "omics-era," theragnostics could become a necessary method, not only in order to improve our knowledge of tumor biology, but also, to find more and more targeted therapies in a multidisciplinary context and in a tailor-based approach.

Tailored Molecular Imaging of Pheochromocytoma and Paraganglioma: Which Tracer and When.

Pheochromocytoma (PCC) and paraganglioma (PGL) are rare neoplasms that fall within the category of neuroendocrine tumors. In the last decade, their diagnostic algorithm has been modified to include the evaluation of molecular pathways, genotype, and biochemical phenotype, in order to correctly interpret anatomical and functional imaging results and tailor the best therapeutic choices to patients. More specifically, the identification of germline mutations has led to a three-way cluster classification: pseudo-hypoxic cluster, cluster of kinase receptor signaling and protein translation pathways, and cluster of Wnt-altered pathway. In this context, functional imaging gained a crucial role in the management of these patients in agreement with the ever-growing concept of personalized medicine. In this paper, we provide an overview of three specific molecular pathways targeted by positron-emitting tracers to image PCCs and PGLs: catecholamine metabolism, somatostatin receptors, and glucose uptake. Finally, we recommend different flow charts for use in the selection of tracers for specific clinical scenarios, based on sporadic/inherited tumor and known/unknown mutation status.

Unespected dectection of unruptured brain arteriovenous malformation with 18F-DOPA PET/MR.

Unruptured brain arteriovenous malformations (AVM) have a heterogeneous clinical presentation, mainly related to the presence of intracerebral hemorrhage. We report the diagnosis of AVM in a patient with Parkinson's disease (PD), who undergone positron emission tomography/magnetic resonance imaging (PET/MRI) molecular brain imaging with fluorine-18-dihydroxyphenylalanine (18F-DOPA). This case suggests that AVM may be occasionally recognized in molecular imaging studies using positron-emitting amino acids. Magnetic resonance imaging with susceptibility-weighted imaging (SWI) sequences and 3D time of flight (TOF) reconstruction may contribute to manage patients with AVM.

Biochemical and Pathophysiological Premises to Positron Emission Tomography With Choline Radiotracers.

Choline is a quaternary ammonium base that represents an essential component of phospholipids and cell membranes. Malignant transformation is associated with an abnormal choline metabolism at a higher levels with respect to those exclusively due to cell multiplication. The use of Positron Emission Tomography/Computed Tomography (PET/CT) with radiocholine (RCH), labeled with 11 C or 18 F, is widely diffuse in oncology, with main reference to restaging of patients with prostate cancer. The enhanced concentration in neoplasm is based not only on the increasing growing rate, but also on more specific issues, such as the augmented uptake in malignant cells due to the up-regulation of choline kinase. Furthermore the role of hypoxia in decreasing choline's uptake determine an in vivo concentration only in well oxygenated tumors, with a lower uptake when malignancy increases, that is, in tumors positive at 18 F-Fluoro-deoxyglucose. In this paper we have analyzed the most important issues related to the possible utilization of RCH in diagnostic imaging of human cancer. J. Cell. Physiol. 232: 270-275, 2017. © 2016 Wiley Periodicals, Inc.

Role of Nuclear Sentinel Lymph Node Mapping Compared to New Alternative Imaging Methods.

With the emergence of sentinel node technology, many patients can be staged histopathologically using lymphatic mapping and selective lymphadenectomy. Structural imaging by using US, CT and MR permits precise measurement of lymph node volume, which is strongly associated with neoplastic involvement. Sentinel lymph node detection has been an ideal field of application for nuclear medicine because anatomical data fails to represent the close connections between the lymphatic system and regional lymph nodes, or, more specifically, to identify the first draining lymph node. Hybrid imaging has demonstrated higher accuracy than standard imaging in SLN visualization on images, but it did not change in terms of surgical detection. New alternatives without ionizing radiations are emerging now from "non-radiological" fields, such as ophthalmology and dermatology, where fluorescence or opto-acoustic imaging, for example, are widely used. In this paper, we will analyze the advantages and limits of the main innovative methods in sentinel lymph node detection, including innovations in lymphoscintigraphy techniques that persist as the gold standard to date.

Radiomics in Breast Imaging: Future Development.

Breast cancer is the most common and most commonly diagnosed non-skin cancer in women. There are several risk factors related to habits and heredity, and screening is essential to reduce the incidence of mortality. Thanks to screening and increased awareness among women, most breast cancers are diagnosed at an early stage, increasing the chances of cure and survival. Regular screening is essential. Mammography is currently the gold standard for breast cancer diagnosis. In mammography, we can encounter problems with the sensitivity of the instrument; in fact, in the case of a high density of glands, the ability to detect small masses is reduced. In fact, in some cases, the lesion may not be particularly evident, it may be hidden, and it is possible to incur false negatives as partial details that may escape the radiologist's eye. The problem is, therefore, substantial, and it makes sense to look for techniques that can increase the quality of diagnosis. In recent years, innovative techniques based on artificial intelligence have been used in this regard, which are able to see where the human eye cannot reach. In this paper, we can see the application of radiomics in mammography.

The Role of Imaging of Lymphatic System to Prevent Cancer Related Lymphedema.

Lymphedema is a progressive chronic condition affecting approximately 250 million people worldwide, a number that is currently underestimated. In Western countries, the most common form of lymphedema of the extremities is cancer-related and less radical surgical intervention is the main option to prevent it. Standardized protocols in the areas of diagnosis, staging and treatment are strongly required to address this issue. The aim of this study is to review the main diagnostic methods, comparing new emerging procedures to lymphoscintigraphy, considered as the golden standard to date. The roles of Magnetic Resonance Lymphangiography (MRL) or indocyanine green ICG lymphography are particularly reviewed in order to evaluate diagnostic accuracy, potential associations with lymphoscintigraphy, and future directions guided by AI protocols. The use of imaging to treat lymphedema has benefited from new techniques in the area of lymphatic vessels anatomy; these perspectives have become of value in many clinical scenarios to prevent cancer-related lymphedema.

Breast Imaging Physics in Mammography (Part II).

One of the most frequently detected neoplasms in women in Italy is breast cancer, for which high-sensitivity diagnostic techniques are essential for early diagnosis in order to minimize mortality rates. As addressed in Part I of this work, we have seen how conditions such as high glandular density or limitations related to mammographic sensitivity have driven the optimization of technology and the use of increasingly advanced and specific diagnostic methodologies. While the first part focused on analyzing the use of a mammography machine from a physical and dosimetric perspective, in this paper, we will examine other techniques commonly used in breast imaging: contrast-enhanced mammography, digital breast tomosynthesis, radio imaging, and include some notes on image processing. We will also explore the differences between these various techniques to provide a comprehensive overview of breast lesion detection techniques. We will examine the strengths and weaknesses of different diagnostic modalities and observe how, with the implementation of improvements over time, increasingly effective diagnoses can be achieved.

Breast Imaging Physics in Mammography (Part I).

Breast cancer is the most frequently diagnosed neoplasm in women in Italy. There are several risk factors, but thanks to screening and increased awareness, most breast cancers are diagnosed at an early stage when surgical treatment can most often be conservative and the adopted therapy is more effective. Regular screening is essential but advanced technology is needed to achieve quality diagnoses. Mammography is the gold standard for early detection of breast cancer. It is a specialized technique for detecting breast cancer and, thus, distinguishing normal tissue from cancerous breast tissue. Mammography techniques are based on physical principles: through the proper use of X-rays, the structures of different tissues can be observed. This first part of the paper attempts to explain the physical principles used in mammography. In particular, we will see how a mammogram is composed and what physical principles are used to obtain diagnostic images.

Automated 3D Ultrasound as an Adjunct to Screening Mammography Programs in Dense Breast: Literature Review and Metanalysis.

Purpose: The purpose of this meta-analysis is to investigate the effectiveness of supplementing screening mammography with three-dimensional automated breast ultrasonography (3D ABUS) in improving breast cancer detection rates in asymptomatic women with dense breasts. Materials and Methods: We conducted a thorough review of scientific publications comparing 3D ABUS and mammography. Articles for inclusion were sourced from peer-reviewed journal databases, namely MEDLINE (PubMed) and Scopus, based on an initial screening of their titles and abstracts. To ensure a sufficient sample size for meaningful analysis, only studies evaluating a minimum of 20 patients were retained. Eligibility for evaluation was further limited to articles written in English. Additionally, selected studies were required to have participants aged 18 or above at the time of the study. We analyzed 25 studies published between 2000 and 2021, which included a total of 31,549 women with dense breasts. Among these women, 229 underwent mammography alone, while 347 underwent mammography in combination with 3D ABUS. The average age of the women was 50.86 years (±10 years standard deviation), with a range of 40-56 years. In our efforts to address and reduce bias, we applied a range of statistical analyses. These included assessing study variation through heterogeneity assessment, accounting for potential study variability using a random-effects model, exploring sources of bias via meta-regression analysis, and checking for publication bias through funnel plots and the Egger test. These methods ensured the reliability of our study findings. Results: According to the 25 studies included in this metanalysis, out of the total number of women, 27,495 were diagnosed with breast cancer. Of these, 211 were diagnosed through mammography alone, while an additional 329 women were diagnosed through the combination of full-field digital mammography (FFDSM) and 3D ABUS. This represents an increase of 51.5%. The rate of cancers detected per 1000 women screened was 23.25‱ (95% confidence interval [CI]: 21.20, 25.60; p < 0.001) with mammography alone. In contrast, the addition of 3D ABUS to mammography increased the number of tumors detected to 20.95‱ (95% confidence interval [CI]: 18.50, 23; p < 0.001) per 1000 women screened. Discussion: Even though variability in study results, lack of long-term outcomes, and selection bias may be present, this systematic review and meta-analysis confirms that supplementing mammography with 3D ABUS increases the accuracy of breast cancer detection in women with ACR3 to ACR4 breasts. Our findings suggest that the combination of mammography and 3D ABUS should be considered for screening women with dense breasts. Conclusions: Our research confirms that adding 3D automated breast ultrasound to mammography-only screening in patients with dense breasts (ACR3 and ACR4) significantly (p < 0.05) increases the cancer detection rate.

[Dw-MRI and bone scintigraphy in monitoring radio-therapy response in bone metastases]. / DW-MRI e scintigrafia ossea con difosfonati nella valutazione del trattamento con radioterapia a fasci esterni delle metastasi ossee.

Bone is one of the most common sites of metastatic spread of malignancy, with possible deleterious effects including pain, hypercalcemia, and pathologic fracture. External beam radiotherapy (EBRT) remains the mainstay for treatment of painful bone metastases. Diffusion-weighted MRI (DW-MRI) has been described as an efficient method to differentiate good and poor responders to radiotherapy in bone metastases patients. The addition of DWI to conventional whole-body MRI sequences enhanced lesion conspicuity and improved diagnostic accuracy. We evaluate bone metastases patients with bone scintigraphy and DW-MRI. With technical optimization, whole-body MRI with DWI, as a nonionizing imaging modality, may potentially be useful as an alternative method to bone scintigraphy in the management of bone metastases.

[Inflammatory bowel disease: possibilities and limits in multidetector computed tomography]. / La malattia infiammatoria intestinale: possibilità e limiti della enteroclisi TC.

Technical advances in computed tomography (CT), including helical CT and multidetector CT, have resulted in an improved ability to evaluate the small intestine. CT examination of the small bowel requires the use of dedicated techniques for optimal evaluation of inflammatory bowel disease in order to select the most appropriate therapeutic strategy for the individual patient and to monitor disease progression over time.Although intraluminal contrast media combined with intravenous iodinated contrast agents with a biphasic injection protocol provide good visualization of the typical lesions of the disease, accurate estimation of the degree of disease activity can only be achieved with nuclear imaging. Owing to continuous technical improvements, magnetic resonance imaging is expected to play an increasing role in the near future. However, in selected patients, three-dimensional endoanal ultrasonography remains the gold standard technique for assessing the anal sphincter and the recto-anal junction.

[Actual role of MR in the small bowel studies: dynamic sequences and bowel distension]. / Attuali possibilità della RM nello studio dell'intestino tenue: sequenze dinamiche e distensione digiuno-ileale.

Magnetic resonance (MR) is even more becoming important in the evaluation of the small bowel, thanks to the technologic advances of the machines and thanks to the improvement of specific diagnostic protocols of study. MR is a pivotal in identifying acute stenosis and alterations of the bowel wall and in differentiating between inflammatory and fibrotic alterations. Diffusion techniques and dynamic MRI allows the assessment of the degree of disease activity of IBD, although nuclear medicine represents the gold standard.

[Gastroenteric diseases in the third millennium: a rational approach to optimal imaging technique and patient selection]. / La patologia intestinale nel terzo millennio: la scelta della metodica e la selezione del paziente nella gestione dell'approccio razionale all'imaging.

In the last twenty years, the study of gastroenteric disorders underwent a radical change as a result of rapid advances in diagnostic imaging, with the introduction of more sophisticated and better performing techniques. Although this evolution has significantly contributed to improve diagnostic accuracy, also allowing assessment of different areas of the gastroenteric tract that could not be well evaluated in the past, clinicians may feel confused about deciding the most appropriate diagnostic approach according to lesion type and site. The aim of this paper is to provide an overview of available imaging techniques to guide the diagnostic approach to gastroenteric diseases.

[Role of nuclear imaging in the management and follow-up of patients with inflammatory bowel disease]. / Ruolo delle tecniche di medicina nucleare nella programmazione terapeutica e nel follow-up della malattia infiammatoria intestinale.

The modern approach to diagnostic imaging includes multimodal evaluation of patients. Physician knowledge of the clinical potential of each available imaging technique combined with efficient integration of functional and morphological data is mandatory in order to achieve a timely diagnosis and treatment, and to avoid unnecessary invasive examinations. Recent years have witnessed important advances in nuclear medicine techniques, including the development of a great variety of metabolic tracers that allow accurate detection, characterization and staging of diverse disease states other than neoplastic conditions. Nuclear medicine techniques play an important role in the diagnostic evaluation of different forms of inflammatory bowel disease (Crohn's disease, ulcerative rettocolitis, indeterminate colitis), and can provide optimal anatomo-functional information when used in association with multidetector CT and MRI, enabling tailored therapeutic interventions.

[Evaluation of the small bowel with computed tomography enteroclysis: technical applications and clinical indications]. / La valutazione del piccolo intestino con radiologia computerizzata: l'enteroclisi TC. Tecnica di esecuzione ed indicazioni cliniche.

CT enteroclysis is an imaging technique that allows better visualization of the small bowel than standard abdomino-pelvic CT. It is more accurate than CT enterography and provides complementary diagnostic information to digestive endoscopy. Multiplanar reconstruction allows better evaluation of the diseases arising from the small bowel wall, or from surrounding organs, resulting in increased accuracy and effectiveness of this imaging technique. CT enteroclysis often enables a comprehensive assessment of small bowel disease, allowing a definite diagnosis and characterization of intestinal bowel disease, or of other related pathological conditions.

Inflammatory bowel disease: value in diagnosis and management of MDCT-enteroclysis and 99mTc-HMPAO labeled leukocyte scintigraphy.

OBJECTIVES: The aims of this study are: (a) to evaluate the reliability of Multidetector Computed Tomography Enteroclysis (MDCT-E) and (99m)Tc-HMPAO labeled leukocyte scintigraphy (TLLS), in inflammatory bowel disease, (b) to test the accuracy of the two techniques with regard to their histological results, (c) to define how each technique can influence the natural course of inflammatory bowel disease (IBD), (d) to assess the potential value of the two techniques combined. MATERIALS AND METHODS: Thirty-seven patients with suspected IBD underwent MDCT-E and TLLS. We made a separate assessment of the results shown by the two methods and then compared and contrasted the histological results of the two. The latter, however, were either disappointing or not available in 15 patients who, for this reason, had to be dismissed from the study. As result, the number of participants eventually dropped to 22 subjects: 12 women, 10 men with an average age of 44 years. RESULTS: MDCT-E and TLLS were successful in all patients. Sensitivity, specificity, and efficiency values have been reported as follows: MDCT-E: 62%, 100%, 64%,100%, 11%, respectively. TLLS: 90%, 100%, 91%, 100%, 33%, respectively. The two methods combined: 95%, 100%, 95%, 100%, 50%, respectively. CONCLUSIONS: The two techniques can be employed in different stages of the natural course of the disease. In our experience, TLLS proved itself to be useful in the diagnosis of the disease and the assessment of its development. Conversely, MDCT-E proved itself to be more reliable in identifying the seat and the extent of the disease inside and outside the bowel wall as well as potential intra-peritoneal and extra-intestinal complications. The combined use of the two methods represents the Criterion Standard for diagnosing IBD with imaging.

FDG-CT/PET false positive case in hip prosthesis: a clue to avoid error.

A 62 years old woman 6 months after left total hip prosthesis referred to our institution for persistent pain and warm, stiff, and swollen joint. 18F-FDG CT/PET Images showed an intense focal uptake corresponding to the external margin of inter-trochanteric region of prosthesis and inside the stem inferiorly, but common decision was to reconstruct PET images without attenuation correction and now showed a complete and unexpected disappearance of focal and pathological FDG uptake. This case shows the potential propagation of CT artifacts into PET emission data close to metal implants and should be taken in account together to SUV values.

The Role of Molecular Imaging in a Muscle-Invasive Bladder Cancer Patient: A Narrative Review in the Era of Multimodality Treatment.

Diagnostic imaging in bladder cancer plays an important role since it is needed from pretreatment staging to follow-up, but a morphological evaluation performed with both CT and MRI showed low sensitivities and specificities in detecting pathologic lymph nodes, due to the occurrence of false positive results. Implementation of functional information provided by PET/CT could be a determinant in the management of patients with muscle-invasive bladder cancer. A focus on the role of 18F-FDG PET/CT and alternative tracers in patients with muscle-invasive bladder cancer is provided in this analysis in order to outline its potential applications in staging settings and response evaluation after neoadjuvant chemotherapy.

Second-Generation 3D Automated Breast Ultrasonography (Prone ABUS) for Dense Breast Cancer Screening Integrated to Mammography: Effectiveness, Performance and Detection Rates.

In our study, we added a three-dimensional automated breast ultrasound (3D ABUS) to mammography to evaluate the performance and cancer detection rate of mammography alone or with the addition of 3D prone ABUS in women with dense breasts. Our prospective observational study was based on the screening of 1165 asymptomatic women with dense breasts who selected independent of risk factors. The results evaluated include the cancers detected between June 2017 and February 2019, and all surveys were subjected to a double reading. Mammography detected four cancers, while mammography combined with a prone Sofia system (3D ABUS) doubled the detection rate, with eight instances of cancer being found. The diagnostic yield difference was 3.4 per 1000. Mammography alone was subjected to a recall rate of 14.5 for 1000 women, while mammography combined with 3D prone ABUS resulted in a recall rate of 26.6 per 1000 women. We also observed an additional 12.1 recalls per 1000 women screened. Integrating full-field digital mammography (FFDM) with 3D prone ABUS in women with high breast density increases and improves breast cancer detection rates in a significant manner, including small and invasive cancers, and it has a tolerable impact on recall rate. Moreover, 3D prone ABUS performance results are comparable with the performance results of the supine 3D ABUS system.