This comprehensive review examines the current status of ultrasonographic hepatic fat quantification following the nomenclature change from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD). Recent studies have demonstrated that severe steatosis (magnetic resonance imaging-proton density fat fraction: MRI-PDFF ≥17.1%) accelerates fibrosis progression in early-stage MASLD, reestablishing the clinical significance of hepatic fat quantification in this globally prevalent condition affecting 25% of the population. While the reference standard has evolved from invasive liver biopsy to MRI-PDFF, cost and throughput limitations have led to the development of ultrasound attenuation methods for clinical practice. Four techniques have been developed and validated in Japan through large-scale multicenter studies: controlled attenuation parameter (CAP), ultrasound-guided attenuation parameter (UGAP), attenuation measurement (iATT), and attenuation imaging (ATI). Comparative analyses revealed significantly superior correlations with MRI-PDFF for B-mode-guided methods (UGAP: r = 0.798, iATT: r = 0.761, ATI: r = 0.765) compared to CAP (r = 0.662). Diagnostic performance (area under the receiver operating characteristic curve: AUROC) was similarly superior for the three B-mode-guided techniques (0.896-0.919) versus CAP (0.865). The Japan Society of Ultrasonics in Medicine revised its diagnostic criteria in 2021, transitioning from subjective evaluation to objective quantitative assessment using attenuation coefficients. Clinical implementation has accelerated following insurance coverage approval for CAP (2022) and iATT/ATI (2024). Technically, CAP (A-mode) offers simplicity but susceptibility to vascular interference, while B-mode-guided methods provide anatomical precision with inherent operator dependency. Future developments include combined multiple ultrasonic parameters and machine learning integration for enhanced diagnostic accuracy. Ultrasound attenuation methods represent noninvasive, repeatable technologies that improve patient motivation and enable personalized medicine, positioning them as central tools in contemporary hepatology practice.

The identification and accurate diagnosis of focal liver lesions are important in modern medicine, where diagnostic radiology plays an essential role. This review aimed to examine the hyperechogenicity and histopathological features of focal liver lesions. Hyperechogenic liver lesions can be either benign or malignant. Evidence shows that hyperechogenicity is caused by factors such as fat deposition, sinusoidal dilation, peliotic changes, and pseudoglandular patterns. Fat deposition is a common cause of increased echogenicity in hepatocellular carcinoma (HCC). Meanwhile, sinusoidal dilation and peliotic changes are more frequently observed in larger HCC nodules. Pseudoglandular patterns, characterized by the reflection of ultrasound waves at the walls of numerous acini, are associated with hyperechogenicity in well-to-moderately differentiated HCCs. Moreover, this review comprehensively examined the histological features that may cause hyperechogenic internal echoes in not only HCCs but also localized liver lesions (metastases of adenocarcinoma and neuroendocrine neoplasm, intrahepatic cholangiocarcinoma, cavernous hemangioma, focal nodular hyperplasia, and angiomyolipoma). To make an accurate diagnosis and provide appropriate management, it is important to understand the histopathological basis for hyperechogenicity in focal liver lesions. By maximizing the accuracy of imaging studies and enhancing the radiology-pathology correlation, unnecessary biopsies can be avoided, thereby reducing potential complications and mortality. This review can help facilitate the effective management of patients with focal liver lesions, thereby resulting in timely and appropriate treatment decision-making.

Purpose: We previously developed a novel therapy with low-intensity pulsed ultrasound (LIPUS) that ameliorates cognitive decline through upregulation of endothelial nitric oxide synthase (eNOS) in mouse models of Alzheimer’s disease (AD). In a randomized, double-blind, placebo-controlled pilot trial, we demonstrated that whole-brain LIPUS therapy is safe and tends to suppress the cognitive decline in early AD patients. We herein report the findings of our basic experiments that we performed for the pilot trial in order to apply whole-brain LIPUS therapy to humans, as well. Methods: First, we examined the relationship between bone density/thickness and ultrasound transmittance using human temporal bone. Next, based on the results of ultrasound transmittance, we further examined mRNA expression of VEGF, FGF2, and eNOS in response to variable ultrasound frequencies, duty cycles, and sound pressures. Results: There was a significant correlation between bone thickness and transmittance (1.0 MHz, P < 0.001), while there was no significant correlation between bone density and transmittance (1.0 MHz, P = 0.421). At a frequency of 0.5 MHz, the optimum duty cycle was considered to be up to 20%. When the tissue amplitude was in the range of 0.05-0.5 MPa, VEGF, FGF2, and eNOS were significantly upregulated by LIPUS. Thus, the conditions necessary for LIPUS therapy for the human brain were identified as sound pressure just below the probe 1.3 MPa (tissue amplitude 0.15 MPa), duty cycle 5%, and frequency 0.5 MHz. Conclusion: We successfully identified the optimal treatment conditions for LIPUS therapy for patients with AD.

There are many reported cases of pancreatic carcinoma in situ discovered based on focal pancreatic parenchymal atrophy detected on CT or MRI. However, there have been no reports of US findings to date, and US characteristics remain unclear. We report a case of pancreatic carcinoma in situ discovered based on screening US revealing focal pancreatic parenchymal atrophy. The patient was a male in his sixties. During his hospitalization for lung abscess, US screening revealed focal pancreatic parenchymal atrophy, main pancreatic duct stenosis, and distal pancreatic duct dilatation. There was no interruption of the main pancreatic duct wall or a mass. Therefore, pancreatic carcinoma in situ was suspected. Pancreatic cancer was suspected based on CT, MRI, EUS, and ERCP, and atypical cells were detected at serial pancreatic juice aspiration cytologic examination (SPACE), so a distal pancreatectomy was performed. The final diagnosis was stage 0 pancreatic carcinoma in situ. It has been reported that focal pancreatic parenchymal atrophy appears earlier than main pancreatic duct dilatation at the stage of carcinoma in situ. An unnatural concave contour on the long-axis view of the pancreas on US can be recognized as focal pancreatic parenchymal atrophy. If this finding can be detected on US during a health checkup, it is expected that many cases of stage 0 pancreatic cancer could be discovered.