Search Results (216)

Prostate cancer diagnostics have evolved substantially with the integration of multiparametric magnetic resonance imaging (mpMRI), refined prostate-specific antigen (PSA) metrics, and targeted biopsy techniques. While mpMRI has become a central gatekeeper in biopsy decision-making, it is not infallible. Clinically significant prostate cancer may therefore remain undetected, particularly in patients with elevated PSA density, adverse PSA kinetics, or MRI-occult disease. This narrative review synthesizes contemporary evidence on PSA interpretation, mpMRI performance, and biopsy strategy selection, highlighting the limitations of single-parameter approaches. We discuss the diagnostic yield and clinical implications of targeted, systematic, and combined biopsy techniques, emphasizing scenarios in which systematic sampling remains necessary despite negative or equivocal imaging findings. Emerging data support combined targeted and systematic biopsy as the most robust strategy for maximizing the detection of clinically significant disease while limiting overdiagnosis in most biopsy-naive and high-risk patients. By integrating PSA dynamics, prostate volume, imaging findings, and individual risk profiles, a structured, risk-adapted diagnostic pathway can be achieved. The proposed framework is intended as a conceptual, expert-derived clinical aid to support risk-adapted decision-making. It should be interpreted alongside established guidelines, and prospective validation in future studies is warranted. Full article

Prostate cancer (PCa) is the most common malignancy in men worldwide. Multiparametric MRI (mpMRI) improves the detection of clinically significant PCa (csPCa); however, it remains limited by false-positive findings and inter-observer variability. Time-dependent diffusion (TDD) MRI provides microstructural information that may enhance csPCa characterization beyond standard mpMRI. This prospective observational diagnostic accuracy study protocol describes the evaluation of PROS-TD-AI, an in-house developed AI workflow integrating TDD-derived metrics for zone-aware csPCa risk prediction. PROS-TD-AI will be compared with PI-RADS v2.1 in routine clinical imaging using MRI-targeted prostate biopsy as the reference standard. Full article

Background/Objectives: The transperineal (TP) approach has progressively replaced the transrectal (TR) approach for prostate biopsy because of its improved safety profile. However, its impact on the detection of clinically significant prostate cancer (csPCa), particularly within modern lesion-focused biopsy strategies that combine targeted and perilesional sampling, remains uncertain. We aimed to evaluate the real-world diagnostic impact of transitioning from a TR systematic-based biopsy strategy to a TP lesion-focused approach. Methods: We conducted a retrospective single-centre study including consecutive men who underwent image-guided prostate biopsy between 2018 and 2025. Only patients with a single MRI-visible lesion (PI-RADS ≥ 3) were included. Two biopsy strategies were compared: TR systematic biopsy (TR–SBx), combining targeted and systematic cores, and TP lesion-focused biopsy (TP–LFx), combining targeted and perilesional cores. The primary outcome was the detection of csPCa (Gleason Grade Group ≥ 2). Secondary outcomes included detection of Gleason Grade Group 1 cancer and negative biopsies. Inverse probability of treatment weighting (IPTW) based on a propensity score was applied to adjust for baseline differences. Doubly robust weighted logistic regression models were used, with predefined subgroup and sensitivity analyses. Results: Among 1032 included patients, 931 underwent TR–SBx and 101 TP–LFx. After restriction to the region of common support, 528 patients were retained for IPTW analyses. In the IPTW-adjusted analysis, TP–LFx was associated with higher csPCa detection compared with TR–SBx (adjusted odds ratio [OR] 2.52, 95% confidence interval [CI] 1.40–4.52; p = 0.002) and with lower detection of Gleason Grade Group 1 cancer (OR 0.50, 95% CI 0.27–0.92; p = 0.03). Subgroup analyses suggested a stronger association in patients with prior negative biopsy and in anterior or apical lesions. Conclusions: In routine clinical practice, transitioning from a transrectal systematic-based biopsy strategy to a transperineal lesion-focused approach was associated with improved detection of csPCa and reduced overdiagnosis. These findings support the consideration of transperineal, lesion-focused MRI-guided biopsy strategies in contemporary prostate cancer diagnostics. Full article

The “Neuroimaging and Pathology Biomarkers in Parkinson’s Disease” course held on 12–13 September 2025 in Milan, Italy, convened an international faculty to review state-of-the-art biomarkers spanning neurotransmitter dysfunction, protein pathology and clinical translation. Here, we synthesize the four themed sessions and highlights convergent messages for diagnosis, stratification and trial design. The first session focused on neuroimaging markers of neurotransmitter dysfunction, highlighting how positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) provided complementary insights into dopaminergic, noradrenergic, cholinergic and serotonergic dysfunction. The second session addressed in vivo imaging of protein pathology, presenting recent advances in PET ligands targeting α-synuclein, progress in four-repeat tau imaging for progressive supranuclear palsy and corticobasal syndromes, and the prognostic relevance of amyloid imaging in the context of mixed pathologies. Imaging of neuroinflammation captures inflammatory processes in vivo and helps study pathophysiological effects. The third session bridged pathology and disease mechanisms, covering the biology of α-synuclein and emerging therapeutic strategies, the clinical potential of seed amplification assays and skin biopsy, the impact of co-pathologies on disease expression, and the “brain-first” versus “body-first” model of pathological spread. Finally, the fourth session addressed disease progression and clinical translation, focusing on imaging predictors of phenoconversion from prodromal to clinically overt stages of synucleinopathies, concepts of neural reserve and compensation, imaging correlates of cognitive impairment, and MRI approaches for atypical parkinsonism. Biomarker-informed pharmacological, infusion-based, and surgical strategies, including network-guided and adaptive deep brain stimulation, were discussed as examples of how multimodal biomarkers may inform personalized management. Across all sessions, the need for harmonization, longitudinal validation, and pathology-confirmed outcome measures was consistently emphasized as essential for advancing biomarker qualification in multicentre research and clinical practice. Full article

Background and Objective: Clavicular pain and swelling in children can have multiple causes and often require a multidisciplinary approach. We aimed to describe the characteristics and final diagnoses of children with clavicular involvement and to review the literature on this topic. Methods: We retrospectively reviewed patients younger than 18 years who were evaluated for clavicular symptoms at two pediatric rheumatology centers and one pediatric oncohematology center. These data were then descriptively compared with findings from 63 patients reported across 7 published articles. Results: Twelve patients (9 females, median age 10 years [IQR 9.4–10.5]) were included. Final diagnoses were chronic nonbacterial osteomyelitis (CNO; 8), Langerhans cell histiocytosis (LCH; 2), reactive arthritis (1), and Tietze syndrome (1). Clavicular involvement was mostly unilateral and localized to the medial clavicle in CNO. The most frequent presenting symptom was local swelling (11/12), followed by pain (9/12). Diagnostic delay was a median of 4 months (IQR 1–10.5). Whole-body MRI revealed multifocal lesions in 6/8 CNO patients. Biopsy was often required for diagnosis primarily to exclude malignancy and to clarify atypical or unifocal presentations. The literature review confirmed CNO as the most frequent cause, followed by rare tumors. Conclusions: CNO predominates among pediatric non-traumatic clavicular lesions, but LCH and rare conditions are not uncommon, underscoring the need for careful differential diagnosis and targeted imaging. Full article

Background and Objectives: Lacrimal sac/nasolacrimal duct (LS/NLD) tumors may present as primary acquired nasolacrimal duct obstruction (PANDO), raising debate over routine versus selective dacryocystorhinostomy (DCR) biopsy. We systematically reviewed (i) biopsy yields in routine versus selective strategies, (ii) clinical/imaging red flags for neoplasia, and (iii) outcomes of malignant LS/NLD tumors. Materials and Methods: Following a preregistered PRISMA 2020-compliant protocol, we searched PubMed/MEDLINE, Web of Science, and Scopus (1970–2025) for adult cohorts reporting histopathology, imaging, or oncologic outcomes in PANDO/DCR or LS/NLD tumors. Eligible designs included comparative, cohort, cross-sectional, and diagnostic accuracy studies with histology as a reference. Results: Across 16 cohorts, routine DCR series reported “any specific pathology” in 0–7.91% of specimens and malignant yields generally ≤0.73%. In Anderson, 7.91% of 316 patients had significant pathology and 4.43% neoplasia, with 2.53% unsuspected pre-/intra-operatively. Selective biopsy or tumor-enriched cohorts showed higher malignant burdens; pooled modern data yielded ~72.8% squamous cell carcinoma and ~21.4% lymphoma among malignancies. Imaging red flags included bone erosion (50% malignant vs. 11% benign) and infiltrative patterns (63% vs. 0%), while sac masses were present in 88% of tumors in one recent series. In LSSCC-only cohorts, contemporary multimodal therapy achieved 5-year overall survival of 87.6% and progression-free survival of 76.3%. Conclusions: Malignancy is rare in unselected PANDO but clinically significant when present. A tiered strategy combining bedside red flags, targeted CT/MRI, and selective biopsy appears to balance oncologic safety with resource stewardship and supports histology-directed epithelial versus lymphoma care pathways. Full article

Background and Clinical Significance: Isoechoic renal tumors, defined as masses demonstrating echogenicity similar to normal renal parenchyma, represent a significant diagnostic challenge in contemporary ultrasonographic practice. These lesions, occurring in 5–12% of all renal masses, frequently escape detection on conventional ultrasound, leading to delayed diagnosis and potentially adverse oncological outcomes. Isoechoic renal tumors encompass both benign and malignant entities, with clear cell renal cell carcinoma representing 65–70% of malignant cases. Conventional ultrasound shows limited sensitivity (48–67%) for detecting isoechoic masses, while contrast-enhanced ultrasound achieves detection rates of 94–98%. Multiparametric MRI and dual-energy CT provide superior characterization, with accuracy rates of 85–92% for differentiating benign from malignant lesions. Case Presentation: We describe the case of an 80-year-old male in whom a 2.4 cm isoechoic renal mass was incidentally detected during abdominal ultrasound performed for chronic kidney disease monitoring. Contrast-enhanced CT confirmed a solid, hypervascular lesion with wash-out characteristics. Given the patient’s age, comorbidities, and tumor characteristics, multidisciplinary evaluation led to an active surveillance strategy. At 6-month follow-up, the lesion remained stable. Conclusions: Isoechoic renal tumors require multimodal diagnostic approaches and individualized management strategies. Emerging technologies, including artificial intelligence-enhanced ultrasound systems and radiomic-based decision support tools, are undergoing clinical validation and may improve detection and characterization. Investigational approaches such as liquid biopsy and novel PET tracers targeting carbonic anhydrase IX are in early development. Translation of these technologies into clinical practice will require prospective validation, standardization of protocols, and demonstration of cost-effectiveness. Full article

Breast cancer is one of the most prevalent malignant tumors worldwide, with the highest incidence and mortality among women. Early precise diagnosis and the development of efficient treatment regimens remain major clinical challenges. Harnessing the programmable size, surface chemistry, and tumor microenvironment (TME) responsiveness of nanomaterials, there is tremendous potential for their applications in breast cancer diagnosis and therapy. In the diagnostic arena, nanomaterials serve as core components of novel contrast agents (e.g., gold nanorods, quantum dots, superparamagnetic iron oxide nanoparticles) and biosensing platforms, substantially enhancing the sensitivity and specificity of molecular imaging modalities—such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging (FLI)—and enabling high-sensitivity detection of circulating tumor cells and tumor-derived exosomes, among various liquid biopsy biomarkers. In therapy, nanoscale carriers (e.g., liposomes, polymeric micelles) improve tumor targeting and accumulation efficiency through passive and active targeting strategies, thereby augmenting anticancer efficacy while effectively reducing systemic toxicity. Furthermore, nanotechnology has spurred the rapid advancement of emerging modalities, including photothermal therapy (PTT), photodynamic therapy (PDT), and immunotherapy. Notably, the construction of theranostic platforms that integrate diagnostic and therapeutic units within a single nanosystem enables in vivo, real-time visualization of drug delivery, treatment monitoring, and therapeutic response feedback, providing a powerful toolkit for advancing breast cancer toward personalized, precision medicine. Despite challenges that remain before clinical translation—such as biocompatibility, scalable manufacturing, and standardized evaluation—nanomaterials are undoubtedly reshaping the paradigm of breast cancer diagnosis and treatment. Full article

Background: Long pulse width stimulation (LPWS; 120–150 ms) has the potential to stimulate denervated muscles in persons with spinal cord injury (SCI). We examined whether testosterone treatment (TT) + LPWS would increase skeletal muscle size, leg lean mass and improve overall metabolic health in SCI persons with denervation. We hypothesized that one year of combined TT + LPWS would downregulate gene expression of muscle atrophy and upregulate gene expression of muscle hypertrophy and increase mitochondrial health in SCI persons with lower motor neuron (LMN) injury. Methods: Ten SCI participants with chronic LMN injury were randomized into either 12 months, twice weekly, of TT + LPWS (n = 5) or a TT+ standard neuromuscular electrical stimulation (NMES; n = 5). Measurements were conducted at baseline (week 0), 6 months following training (post-intervention 1), and one week following 12 months of training (post-intervention 2). Measurements included body composition assessment using magnetic resonance imaging (MRI) and dual x-ray absorptiometry (DXA). Metabolic profile assessment encompassed measurements of resting metabolic rate, carbohydrate and lipid profiles. Finally, muscle biopsy was captured to measure RNA signaling pathways and mitochondrial oxidative phosphorylation. Results: Compliance and adherence were greater in the TT + NMES compared to the TT + LPWS group. There was a 25% increase in the RF muscle CSA following P1 measurement in the TT + LPWS group. There was a recognizable non-significant decrease in intramuscular fat in both groups. There was a trend (p = 0.07) of decrease in trunk fat mass following TT + LPWS, with an interaction (p = 0.037) in android lean mass between groups. There was a trend (p = 0.08) in mean differences in DXA-visceral adipose tissue (VAT) between groups at P1 measurements. For genes targeting muscle atrophy, TT + LPWS showed a trending decline in MURF1 and FOXO3 genes returning to similar levels as TT + NMES before 12 months. Conclusions: These pilot data demonstrated the safety of applying LPWS in persons with SCI. Six months of TT + LPWS demonstrated increases in rectus femoris muscle CSA. The effects on muscle size were modest between groups. Signaling pathway analysis suggested downregulation of genes involved in muscle atrophy pathways. Future clinical trials may consider a home-based approach with more frequent applications of LPWS. Full article

Background and Objectives: Multiparametric MRI (mpMRI) has improved prostate cancer (PCa) detection, but the added value of cognitive fusion (CF) over systematic biopsy (SB) remains debated. This prospective study evaluated the diagnostic performance of SB, CF, and their combined use in patients with Prostate Imaging and Reporting Data System (PI-RADS) ≥3 lesions. Materials and Methods: A total of 282 patients underwent mpMRI followed by both SB and CF biopsy. Results: PCa was diagnosed in 154 patients. SB detected 112 cancers (24 ISUP 1 (International Society of Urological Pathology), 88 ISUP ≥ 2), and CF detected 135 cancers (16 ISUP 1, 119 ISUP ≥ 2), while the combined approach detected all 154 cancers (9 ISUP 1, 145 ISUP ≥ 2). CF identified 42 cancers missed by SB, whereas SB identified 19 cancers not detected by CF. CF upgraded 38 patients from low-risk to intermediate-risk (23)/high-risk (15) categories, while SB underestimated disease severity in 41 cases. No major biopsy-related complications were recorded. Conclusions: CF biopsy outperformed SB in detecting clinically significant PCa and improved risk stratification, while the combined approach provided the highest overall diagnostic performance, supporting its use in contemporary PCa assessment. Full article

Introduction: Platelet-derived growth factor receptor beta (PDGFRβ) is a key regulator of fibrogenesis. Non-invasive imaging of PDGFRβ expression may offer a novel approach to assess fibrotic remodeling, particularly in cardiac patients’ post-intervention, where fibrosis poses clinical risk. This study presents the GMP-compliant production of a novel PDGFRβ-targeted PET radiopharmaceutical, [⁶⁸Ga]Ga-DOTA-Z09591 ([⁶⁸Ga]Ga-ATH001), and its preclinical evaluation in mouse and human myocardial tissue, along with initial clinical imaging in patients with ST-elevation myocardial infarction (STEMI). Methods: The precursor was chemically synthesized and radiolabeled with gallium-68 using a fully automated, GMP-compatible system and a pharmaceutical-grade ⁶⁸Ge/⁶⁸Ga generator. Autoradiography, H&E, Sirius Red, Masson’s trichrome, and IHC staining were performed on infarcted mouse hearts and human myocardial biopsies. In vivo PET/MRI with [⁶⁸Ga]Ga-ATH001, ¹⁵O-H₂O, and gadolinium contrast was conducted in STEMI patients one week post-percutaneous coronary intervention. Results: [⁶⁸Ga]Ga-ATH001 was produced with high radiochemical yield and purity. Autoradiography demonstrated specific, receptor-mediated binding of [⁶⁸Ga]Ga-ATH001, co-localizing with PDGFRβ immunoreactivity, collagen deposition, and tissue damage. In STEMI patients, focal tracer uptake was observed in infarcted myocardium correlating with MRI-detected structural abnormalities and perfusion defects on ¹⁵O-H₂O PET. Uptake in unaffected myocardium was low and homogeneous, consistent with minimal physiological PDGFRβ expression. Conclusions: [⁶⁸Ga]Ga-ATH001 was successfully developed and validated for phase 0 clinical study. The tracer demonstrated PDGFRβ-specific binding in human fibrotic myocardium and enabled non-invasive detection of myocardial fibrogenic activity in STEMI patients. These findings support further clinical evaluation of [⁶⁸Ga]Ga-ATH001 as a targeted molecular imaging agent for early assessment of post-infarction fibrosis. Full article

Background/Objectives: Multiparametric MRI (mpMRI) and targeted biopsies have revolutionized prostate cancer (PC) detection through the Prostate Imaging Reporting and Data System (PIRADS). However, the effect of prostate volume on cancer detection and the predictive accuracy of PIRADS in the mpMRI-guided biopsy era remains unclear. The aim was to assess whether prostate volume affects detection rates of clinically significant prostate cancer (CSPC) and high-risk prostate cancer (HRPC) and modifies the predictive performance of the PIRADS score. Methods: We retrospectively analyzed 361 biopsy-naïve men who underwent mpMRI-fusion transperineal biopsies between 2016 and 2023. Lesions graded PIRADS ≥ 3 were targeted alongside systematic sampling. A receiver-operating characteristic (ROC) curve (AUC = 0.74) defined a 44 mL cutoff separating small (<44 mL; n = 160) and large (≥44 mL; n = 193) prostates. Logistic regression and cubic-spline analyses evaluated associations between prostate volume, PIRADS, and cancer outcomes. Results: Any cancer was detected in 74.3% of small versus 35.5% of large prostates (p < 0.001); CSPC in 42.5% vs. 19.6% (p < 0.001); HRPC in 14.3% vs. 5.5% (p < 0.001). Small prostate volume independently predicted any cancer (OR 7.31; 95% CI 4.22–12.7), CSPC (OR 5.08; 95% CI 2.87–8.99), and HRPC (OR 4.50; 95% CI 1.80–11.3). Between 40 and 70 mL, each 10 mL increase in volume reduced CSPC risk by 61% (p = 0.008). Prostate volume significantly modified PIRADS accuracy: in large glands, PIRADS 3 lesions carried only 2% risk for CSPC and 0% for HRPC, while in small prostates, PIRADS 3 conferred a 16.9-fold increased CSPC risk. Conclusions: Prostate volume inversely correlates with cancer detection and aggressiveness. PIRADS performance is volume-dependent; PIRADS 3 lesions in large prostates rarely represent significant cancer and may not warrant biopsy. Full article

Background/Objectives: This study analyzed the impact of operator experience on the detection of PC and csPC using a standardized MRI/TRUS-fusion biopsy protocol in an experienced high-volume center. Methods: Men with mpMRI and subsequent combined TB and SB (2019–2024) using transrectal, software-assisted MRI/TRUS-fusion were retrospectively included. Operators were stratified by experience subgroups (<100 vs. ≥100 procedures). Clinical, MRI, and biopsy data have been assessed. The primary objective was the analysis of the effect of biopsy experience on patient-level PC detection. The secondary objective was the PC detection of PI-RADS and DRE. Results: A total of 683 consecutive patients were included (median age 63 years, median PSA 6.5 ng/mL, and median prostate volume 41 mL). Overall, PC and csPC detection were 67% and 51%, with no significant difference in the operator experience subgroups (p = 0.63; p = 0.23). There were no significant differences for additional csPC detection by SB (7% vs. 5%; p = 0.31) or TB (9% vs. 10%; p = 0.93) in both subgroups. DRE showed limited diagnostic value (SEN 32%, SPE 88%, PPV 74%, NPV 55%) with no significant variation regarding the experience (p = 0.12–1.0). Limitations include a single-center, retrospective design and a lack of a radical prostatectomy specimen. Conclusions: In a standardized MRI-targeted biopsy setting, operator experience seems to have a lower influence on PC or csPC detection. High csPC detection in PI-RADS 4–5 supports a TB-only approach, while low rates in PI-RADS 3 suggest follow-up MRI over immediate biopsy. Limited DRE accuracy highlights its declining role in PC assessment. Full article

In recent years, the medical field has witnessed the rapid expansion and refinement of omics and imaging technologies, which have profoundly transformed patient surveillance and monitoring strategies, with stage-adapted protocols and cross-sectional imaging important in high-risk follow-up. In the melanoma context, diagnostic imaging plays a pivotal role in disease staging, follow-up and evaluation of therapeutic response. Moreover, the emergence of Artificial Intelligence (AI) has further driven the transition toward precision medicine, emphasizing the complexity and individuality of each patient: AI/Radiomics pipelines are increasingly supporting lesion characterization and response prediction within clinical workflows. Consequently, it is essential to emphasize the significant potential of quantitative imaging techniques and radiomic applications, as well as the role of AI in improving diagnostic accuracy and enabling personalized oncologic treatment. Early evidence demonstrates increased sensitivity and specificity, along with a reduction in unnecessary biopsies and imaging procedures, within selected care approaches. In this review, we will outline the current clinical guidelines for the management of melanoma patients and use them as a framework to explore and evaluate advanced imaging approaches and their potential contributions. Specifically, we compare the recommendations of major societies such as NCCN, which advocates more intensive imaging for stages IIB–IV; ESMO and AIOM, which recommend symptom-driven surveillance; and SIGN, which discourages routine imaging in the absence of clinical suspicion. Furthermore, we will describe the latest imaging technologies and the integration of AI-based tools for developing predictive models to actively support therapeutic decision-making and patient care. The conclusions will focus on the prospective role of novel imaging modalities in advancing precision oncology, improving patient outcomes and optimizing the allocation of clinical resources. Overall, the current evidences support a stage-adapted surveillance strategy (ultrasound ± elastography for lymph node regions, targeted brain MRI in high-risk patients, selective use of DECT or total-body MRI) combined with rigorously validated AI-based decision support systems to personalize follow-up, streamline workflows and optimize resource utilization. Full article

Background: Glioblastoma (GBM) remains refractory to chemoradiotherapy. Glial populations—microglia/monocyte-derived macrophages, reactive astrocytes, and the oligodendrocyte lineage—shape both treatment resistance and radiation-related brain injury. Scope: We synthesize how myeloid ontogeny and plasticity, astrocytic hubs (IL-6/STAT3, TGF-β, connexin-43/gap junctions), and oligodendrocyte precursor cells (OPCs)–linked programs intersect with DNA-damage responses, hypoxia-driven metabolism, and extracellular vesicle signaling to support tumor fitness while predisposing normal brain to radiotoxicity. Translational implications: Convergent, targetable pathways (IL-6/JAK–STAT3, TGF-β, chemokine trafficking, DDR/senescence) enable co-design of radiosensitization and neuroprotection. Pragmatic levers include myeloid reprogramming (CSF-1R, CCR2), astrocyte-axis modulation (STAT3, TGF-β, Cx43), and brain-penetrant DDR inhibition (e.g., ATM inhibitors), paired with delivery strategies that raise intratumoral exposure while sparing healthy tissue (focused-ultrasound blood–brain barrier opening, myeloid-targeted dendrimers; Tumor Treating Fields as an approved adjunct therapy). Biomarker frameworks (TSPO-PET, macrophage-oriented MRI radiomics, extracellular vesicle liquid biopsy) can support selection and pharmacodynamic readouts alongside neurocognitive endpoints. Outlook: Timing-aware combinations around radiotherapy and hippocampal/white-matter sparing offer a near-term roadmap for “glia-informed” precision radiotherapy. Full article