Innovations in Positron Emission Tomography and State of the Art in the Evaluation of Breast Cancer Treatment Response.

The advent of hybrid Positron Emission Tomography/Computed Tomography (PET/CT) and PET/Magnetic Resonance Imaging (MRI) scanners resulted in an increased clinical relevance of nuclear medicine in oncology. The use of [18F]-Fluorodeoxyglucose ([18F]FDG) has also made it possible to study tumors (including breast cancer) from not only a dimensional perspective but also from a metabolic point of view. In particular, the use of [18F]FDG PET allowed early confirmation of the efficacy or failure of therapy. The purpose of this review was to assess the literature concerning the response to various therapies for different subtypes of breast cancer through PET. We start by summarizing studies that investigate the validation of PET/CT for the assessment of the response to therapy in breast cancer; then, we present studies that compare PET imaging (including PET devices dedicated to the breast) with CT and MRI, focusing on the identification of the most useful parameters obtainable from PET/CT. We also focus on novel non-FDG radiotracers, as they allow for the acquisition of information on specific aspects of the new therapies.

Diagnosis of cardiac amyloid transthyretin (ATTR) amyloidosis by early (soft tissue) phase [99mTc]Tc-DPD whole body scan: comparison with late (bone) phase imaging.

OBJECTIVES: Although expert consensus recommendations suggest 2-3 h as the time interval between bone-seeking radiotracers injection and acquisition, it has been reported that images obtained early after [99mTc]Tc-HMDP administration are sufficient to diagnose cardiac amyloidosis. We evaluated the diagnostic performance of [99mTc]Tc-DPD early phase whole body scan with respect to late phase imaging. METHODS: We qualitatively and semiquantitatively reviewed [99mTc]Tc-DPD imaging of 53 patients referred for suspect cardiac amyloidosis. Findings of early and late phase images were compared with SPECT results (considered the standard-of-reference) determining sensitivity and specificity for visual analysis of each phase imaging and for each semiquantitative index. RESULTS: SPECT imaging was negative for cardiac accumulation in 25 patients and positive in 28. Visual analysis of early phase whole body scan had an extremely significant capability to predict SPECT results; nevertheless, complete agreement was not reached. Visual analysis of late phase imaging showed slightly better results. Semiquantitative analysis of early phase images, namely heart to mediastinum ratio, performed better than semiquantitative analysis of late phase images. CONCLUSION: Visual analysis of [99mTc]Tc-DPD early phase whole body scan is promising in diagnosing cardiac amyloidosis; further studies are needed to confirm our results in different clinical scenarios. KEY POINTS: • Visual analysis of early phase planar imaging using [99mTc]Tc-DPD is accurate to diagnose cardiac amyloidosis and may be satisfactory at least in frail patients with high cardiac burden of amyloid fibrils.

Early preablation rhTSH-stimulated thyroglobulin predicts outcome of differentiated thyroid cancer (DTC) patients.

AIM: Total thyroidectomy and risk-adapted 131-radioiodine therapy (RaIT) are the treatments of choice in differentiated thyroid cancer (DTC) patients. The response to treatments is assessed 6-12 months after RaIT. However, thyroglobulin (Tg) values obtained just before RaIT also provide reliable informations on patients'outcome. As available data were mostly obtained in hypothyroid status, we evaluated the predictive role of preablation-Tg in patients underwent RaIT after rhTSH stimulation. MATERIAL AND METHODS: We enrolled 299 low-to-intermediate risk DTC patients underwent rhTSH-stimulated RaIT (standard protocol). Serum Tg levels were measured before rhTSH administration (basal Tg), before RaIT (early-stimulated Tg), and 2 days after RaIT (late-stimulated Tg). The early response assessment was done 12 months after RaIT according to 2015 American Thyroid Association (2015 ATA) criteria. RESULTS: Most patients (277/299, 92.6%) had an excellent response (ER) to RaIT, while 15/299 (5.1%) and 7/299 (2.3%) patients showed biochemical incomplete/indeterminate response or persistent structural disease, respectively. At receiver operating characteristic analysis, the optimal cutoff to predict ER was set at 1.55 (AUC = 0.792), 2.6 (AUC = 0.931), and 4.9 (AUC = 0.874) ng/mL, for basal, early-, and late-stimulated Tg, respectively. The overall sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for basal, early-, and late-stimulated Tg were 50%, 96.7%, 93.3%, 55%, and 96.1%; 90.9%, 84.5%, 84.9%, 31.7%, and 99.1%; and 90.9%, 71.8%, 73.2%, 20.4%, and 99%, respectively. In univariate and multivariate logistic regression analysis, early-stimulated Tg cutoff resulted as an independent prognostic marker for predicting ER regardless of gender, age, histotype, histological variant, tumor size, risk classification, and stage of disease. CONCLUSION: Early-stimulated Tg is a reliable diagnostic tool for predicting the response to primary treatment of DTC.

Artificial Neural Networks in Cardiovascular Diseases and its Potential for Clinical Application in Molecular Imaging.

In medical imaging, Artificial Intelligence is described as the ability of a system to properly interpret and learn from external data, acquiring knowledge to achieve specific goals and tasks through flexible adaptation. The number of possible applications of Artificial Intelligence is also huge in clinical medicine and cardiovascular diseases. To describe for the first time in literature, the main results of articles about Artificial Intelligence potential for clinical applications in molecular imaging techniques, and to describe its advancements in cardiovascular diseases assessed with nuclear medicine imaging modalities. A comprehensive search strategy was used based on SCOPUS and PubMed databases. From all studies published in English, we selected the most relevant articles that evaluated the technological insights of AI in nuclear cardiology applications. Artificial Intelligence may improve patient care in many different fields, from the semi-automatization of the medical work, through the technical aspect of image preparation, interpretation, the calculation of additional factors based on data obtained during scanning, to the prognostic prediction and risk-- group selection. Myocardial implementation of Artificial Intelligence algorithms in nuclear cardiology can improve and facilitate the diagnostic and predictive process, and global patient care. Building large databases containing clinical and image data is a first but essential step to create and train automated diagnostic/prognostic models able to help the clinicians to make unbiased and faster decisions for precision healthcare.

Clinical Impact of 18F-FDG PET/CT in the Diagnostic Workup of Pancreatic Ductal Adenocarcinoma: A Systematic Review.

In this review, the performance of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the diagnostic workup of pancreatic ductal adenocarcinoma (PDAC) is evaluated. A comprehensive literature search up to September 2020 was performed, selecting studies with the presence of: sample size ≥10 patients and index test (i.e., "FDG" or "18F-FDG" AND "pancreatic adenocarcinoma" or "pancreas cancer" AND "PET" or "positron emission tomography"). The methodological quality was evaluated using the revised quality assessment of diagnostic accuracy studies (QUADAS-2) tool and presented according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Basic data (authors, year of publication, country and study design), patients' characteristics (number of enrolled subjects and age), disease phase, type of treatment and grading were retrieved. Forty-six articles met the adopted research criteria. The articles were divided according to the considered clinical context. Namely, besides conventional anatomical imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), molecular imaging with FDG PET/CT is an important tool in PDAC, for all disease stages. Further prospective studies will be necessary to confirm the cost-effectiveness of such imaging techniques by testing its real potential improvement in the clinical management of PDAC.

The Additional Value of 18F-FDG PET and MRI in Patients with Glioma: A Review of the Literature from 2015 to 2020.

AIM: Beyond brain computed tomography (CT) scan, Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) hold paramount importance in neuro-oncology. The aim of this narrative review is to discuss the literature from 2015 to 2020, showing advantages or complementary information of fluorine-18 fluorodeoxyglucose (18F-FDG) PET imaging to the anatomical and functional data offered by MRI in patients with glioma. METHODS: A comprehensive Pubmed/MEDLINE literature search was performed to retrieve original studies, with a minimum of 10 glioma patients, published from 2015 until the end of April 2020, on the use of 18F-FDG PET in conjunction with MRI. RESULTS: Twenty-two articles were selected. Combined use of the two modalities improves the accuracy in predicting prognosis, planning treatments, and evaluating recurrence. CONCLUSION: According to the recent literature, 18F-FDG PET provides different and complementary information to MRI and may enhance performance in the whole management of gliomas. Therefore, integrated PET/MRI may be particularly useful in gliomas, since it could provide accurate morphological and metabolic information in one-shoot examination and improve the diagnostic value compared to each of procedures.

Undetectable or low (<1 ng/ml) postsurgical thyroglobulin values do not rule out metastases in early stage differentiated thyroid cancer patients.

BACKGROUND: Differentiated thyroid cancer (DTC) work-up is based on (near)total-thyroidectomy plus thyroid remnant ablation (TRA) with 131-radioiodine in many patients, and long-life follow-up. 131I-post therapy whole body scan (pT-WBS) and serum thyroglobulin (Tg) are used in identifying metastatic patients. Some authors have evaluated the possibility of using post-surgical Tg (ps-Tg) values in deciding for or against TRA. The aim of our study was to verify the diagnostic accuracy of 131I-pT-WBS and SPECT/CT imaging (post-therapeutic imaging) compared to serum Tg levels in detecting metastases in early stage of DTC patients. RESULTS: Post-therapeutic imaging revealed metastases in 82 out of 570 (14.4%) patients. Metastases were successively confirmed by other diagnostic tools or by histology (sensitivity and PPV = 100%). Seventy-three out of 82 patients (90.2%) showed ps-Tg levels ≤1 ng/ml. In fifty-four per cent of patients, serum Tg levels at TRA remained ≤1 ng/ml. CONCLUSION: In conclusion, ps-Tg levels cannot be used in deciding for or against TRA. In early stage of DTC, post-therapeutic imaging (131I-pT-WBS and SPECT/CT) is an accurate method of detecting metastases, also in patients with stimulated serum Tg values ≤1 ng/ml. METHODS: We retrospectively reviewed the records of 570 consecutive patients affected by pT1-pT3 DTC (F = 450, M = 120), referred to our Nuclear Medicine Units in the last five years to perform TRA after (near)-total-thyroidectomy.All patients underwent TRA 3-4 months after thyroid surgery either in euthyroid or in hypothyroid state. Serum Tg values evaluated in post-surgical period and at TRA were matched with post-therapeutic imaging results.

Predictive and prognostic value of left ventricular mechanical dyssynchrony assessed by myocardial perfusion single photon emission computed tomography in asymptomatic patients under hemodialysis.

BACKGROUND: Patients under hemodialysis (HD) have an increased risk of major adverse cardiac events (MACEs). In these patients, myocardial perfusion scintigraphy (MPS) provides useful prognostic information. Left ventricular mechanical dyssynchrony (LVD) has been proven to predict all-cause death in patients under HD. It remains unclear, whether the same prognostic value pertains also to the prediction of MACEs. PATIENTS AND METHODS: Ninety patients under HD (duration range: 2-216 months) with neither history nor symptoms of coronary artery disease at the time of MPS were retrospectively evaluated. All underwent clinical evaluation and MPS with dipyridamole stress test. MPS was reprocessed to derive left ventricular ejection fraction (EF), perfusion scores [summed stress score (SSS) and summed difference score (SDS)] and LVD (phase histogram bandwidth and phase SD).ResultsMACEs were reported in 10 (11.1%) patients as assessed at more than 2 years of follow-up (median 29 months). At univariate analysis, a correlation was demonstrated between MACEs and LVD (P<0.001), BMI (P=0.04), ECG changes during stress (P=0.03), dyspnea (P=0.02), SSS (P=0.04) and SDS (P=0.02). At stepwise multivariate analysis, only LVD (P<0.001), SSS (P=0.01) and SDS (P=0.001) were independent predictors of MACEs. No thresholds of SSS or SDS showed predictive value (P=0.79 for SSS ≥4, P=0.10 for SSS >8 and P=0.66 for SDS ≥2). At survival analysis, patients with LVD had a significantly shorter MACE-free survival (P<0.001). This predictive value held true even in patients with an unremarkable pattern of perfusion. CONCLUSION: In asymptomatic patients without known coronary artery disease under HD, LVD is highly predictive of the onset of MACEs at more than 2 years of follow-up and provides incremental value over perfusion scores alone. A phase analysis on gated MPS should be routinely performed in these patients to yield useful prognostic information.