Gold Nanorod-Loaded Nano-Contrast Agent with Composite Shell-Core Structure for Ultrasonic/Photothermal Imaging-Guided Therapy in Ischemic Muscle Disorders.

Purpose: This study aims to broaden the application of nano-contrast agents (NCAs) within the realm of the musculoskeletal system. It aims to introduce novel methods, strategies, and insights for the clinical management of ischemic muscle disorders, encompassing diagnosis, monitoring, evaluation, and therapeutic intervention. Methods: We developed a composite encapsulation technique employing O-carboxymethyl chitosan (OCMC) and liposome to encapsulate NCA-containing gold nanorods (GNRs) and perfluoropentane (PFP). This nanoscale contrast agent was thoroughly characterized for its basic physicochemical properties and performance. Its capabilities for in vivo and in vitro ultrasound imaging and photothermal imaging were authenticated, alongside a comprehensive biocompatibility assessment to ascertain its effects on microcirculatory perfusion in skeletal muscle using a murine model of hindlimb ischemia, and its potential to augment blood flow and facilitate recovery. Results: The engineered GNR@OCMC-liposome/PFP nanostructure exhibited an average size of 203.18±1.49 nm, characterized by size uniformity, regular morphology, and a good biocompatibility profile. In vitro assessments revealed NCA's potent photothermal response and its transformation into microbubbles (MBs) under near-infrared (NIR) irradiation, thereby enhancing ultrasonographic visibility. Animal studies demonstrated the nanostructure's efficacy in photothermal imaging at ischemic loci in mouse hindlimbs, where NIR irradiation induced rapid temperature increases and significantly increased blood circulation. Conclusion: The dual-modal ultrasound/photothermal NCA, encapsulating GNR and PFP within a composite shell-core architecture, was synthesized successfully. It demonstrated exceptional stability, biocompatibility, and phase transition efficiency. Importantly, it facilitates the encapsulation of PFP, enabling both enhanced ultrasound imaging and photothermal imaging following NIR light exposure. This advancement provides a critical step towards the integrated diagnosis and treatment of ischemic muscle diseases, signifying a pivotal development in nanomedicine for musculoskeletal therapeutics.

Using Chiral Auxiliaries to Mimic the Effect of Chiral Media on the Structure of Lanthanide(III) Complexes Common in Bioimaging and Diagnostic MRI.

[Ln·DOTA]- complexes and systems derived therefrom are commonly used in MRI and optical bioimaging. These lanthanide(III) complexes are chiral, and, in solution, they are present in four forms, with two sets of enantiomers, with the ligand donors arranged in either a square antiprismatic, SAP, or twisted square antiprismatic geometry, TSAP. This complicated speciation is found in laboratory samples. To investigate speciation in biological media, when Ln·DOTA-like complexes interact with chiral biomolecules, six Eu·DOTA-monoamide complexes were prepared and investigated by using 1D and 2D 1H NMR. To emulate the chirality of biological media, the amide pendant arm was modified with one or two chiral centers. It is known that a chiral center on the DOTA scaffold significantly influences the properties of the system. Here, it was found that chirality much further away from the metal center changes the available conformational space and that both chiral centers and amide cis/trans isomerism may need to be considered─a fact that, for the optically enriched materials, led to the conclusion that eight chemically different forms may need to be considered, instead of the four forms necessary for DOTA. The results reported here clearly demonstrate the diverse speciation that must be considered when correlating an observation to a structure of a lanthanide(III) complex.

Adding quantitative T1rho-weighted imaging to conventional MRI improves specificity and sensitivity for differentiating malignant from benign breast lesions.

OBJECTIVES: To investigate the feasibility of T1rho-weighted imaging in differentiating malignant from benign breast lesions and to explore the additional value of T1rho to conventional MRI. MATERIALS AND METHODS: We prospectively enrolled consecutive women with breast lesions who underwent preoperative T1rho-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) between November 2021 and July 2023. The T1rho, apparent diffusion coefficient (ADC), and semi-quantitative parameters from DCE-MRI were obtained and compared between benign and malignant groups. The diagnostic performance was analyzed and compared using receiver operating characteristic (ROC) curves and the Delong Test. RESULTS: This study included 113 patients (74 malignant and 39 benign lesions). The mean T1rho value in the benign group (92.61 ± 22.10 ms) was significantly higher than that in the malignant group (72.18 ± 16.37 ms) (P < 0.001). The ADC value and time to peak (TTP) value in the malignant group (1.13 ± 0.45 and 269.06 ± 106.01, respectively) were lower than those in the benign group (1.57 ± 0.45 and 388.30 ± 81.13, respectively) (all P < 0.001). T1rho combined with ADC and TTP showed good diagnostic performance with an area under the curve (AUC) of 0.896, a sensitivity of 81.0%, and a specificity of 87.1%. The specificity and sensitivity of the combination of T1rho, ADC, and TTP were significantly higher than those of the combination of ADC and TTP (87.1% vs. 84.6%, P < 0.005; 81.0% vs. 77.0%, P < 0.001). CONCLUSION: T1rho-weighted imaging was a feasible MRI sequence for differentiating malignant from benign breast lesions. The combination of T1rho, ADC and TTP could achieve a favorable diagnostic performance with improved specificity and sensitivity, T1rho could serve as a supplementary approach to conventional MRI.

Magnetic Resonance Angiography with Hour-Scale Duration after Single Low-Dose Administration of Biocompatible Gadolinium Oxide Nanoprobe.

Long-term contrast-enhanced angiography offers significant advantages in theranostics for diverse vascular diseases, particularly in terms of real-time dynamic monitoring during acute vascular events; However, achieving vascular imaging with a duration of hours through a single administration of low-dose contrast agent remains challenging. Herein, a hyaluronic acid-templated gadolinium oxide (HA@Gd2O3) nanoprobe-enhanced magnetic resonance angiography (MRA) is proposed to address this bottleneck issue for the first time. The HA@Gd2O3 nanoprobe synthesized from a facile one-pot biomineralization method owns ultrasmall size, good biocompatibility, optimal circulation half-life (≈149 min), and a relatively high T1 relaxivity (r1) under both clinical 3 T (8.215 mM-1s-1) and preclinical 9.4 T (4.023 mM-1s-1) equipment. The HA@Gd2O3 nanoprobe-enhanced MRA highlights major vessels readily with significantly improved contrast, extended imaging duration for at least 2 h, and ultrahigh resolution of 0.15 mm under 9.4 T, while only requiring half clinical dosage of Gd. This technique can enable rapid diagnosis and real-time dynamic monitoring of vascular changes in a model of acute superior mesenteric vein thrombosis with only a single injection of nanoprobe. The HA@Gd2O3 nanoprobe-enhanced MRA provides a sophisticated approach for long-term (hour scale) vascular imaging with ultrahigh resolution and high contrast through single administration of low-dose contrast agent.

Distinguishing metabolic signals of liver tumors from surrounding liver cells using hyperpolarized 13 C MRI and gadoxetate.

PURPOSE: To use the hepatocyte-specific gadolinium-based contrast agent gadoxetate combined with hyperpolarized (HP) [1-13 C]pyruvate MRI to selectively suppress metabolic signals from normal hepatocytes while preserving the signals arising from tumors. METHODS: Simulations were performed to determine the expected changes in HP 13 C MR signal in liver and tumor under the influence of gadoxetate. CC531 colon cancer cells were implanted into the livers of five Wag/Rij rats. Liver and tumor metabolism were imaged at 3 T using HP [1-13 C] pyruvate chemical shift imaging before and 15 min after injection of gadoxetate. Area under the curve for pyruvate and lactate were measured from voxels containing at least 75% of normal-appearing liver or tumor. RESULTS: Numerical simulations predicted a 36% decrease in lactate-to-pyruvate (L/P) ratio in liver and 16% decrease in tumor. In vivo, baseline L/P ratio was 0.44 ± 0.25 in tumors versus 0.21 ± 0.08 in liver (p = 0.09). Following administration of gadoxetate, mean L/P ratio decreased by an average of 0.11 ± 0.06 (p < 0.01) in normal-appearing liver. In tumors, mean L/P ratio post-gadoxetate did not show a statistically significant change from baseline. Compared to baseline levels, the relative decrease in L/P ratio was significantly greater in liver than in tumors (-0.52 ± 0.16 vs. -0.19 ± 0.25, p < 0.05). CONCLUSIONS: The intracellular hepatobiliary contrast agent showed a greater effect suppressing HP 13 C MRI metabolic signals (through T1 shortening) in normal-appearing liver when compared to tumors. The combined use of HP MRI with selective gadolinium contrast agents may allow more selective imaging in HP 13 C MRI.

LI-RADS threshold growth based on tumor growth rate can improve the diagnosis of hepatocellular carcinoma ≤ 3.0 cm.

OBJECTIVE: Despite the revision of threshold growth (TG) in the Liver Imaging Reporting and Data System (LI-RADS) version 2018, the appropriate time period between the two examinations for TG has not been determined. We compared the accuracy of LI-RADS with TG based on tumor growth rate for the diagnosis of hepatocellular carcinoma (HCC) with that of LI-RADS v2018 based on the original TG. METHODS: Patients who underwent preoperative MRI for focal solid lesions (≤ 3.0 cm) were retrospectively evaluated. Three readers measured the size of each lesion on prior CT/MRI and index MRI, with tumor growth rate defined as the percent change in lesion size per month. In addition to the original TG (≥ 50% size increase within ≤ 6 months), the modified TG based on tumor growth rates ≥ 10%/month (TG-10%), ≥ 20%/month (TG-20%), and ≥ 30%/month (TG-30%) were evaluated. The accuracies of these evaluation methods for LI-RADS category 5 HCC were compared using generalized estimation equations. RESULTS: A total of 508 lesions from 370 patients were evaluated. Compared with LI-RADS v2018 with the original TG, the accuracy of LI-RADS with TG-10% was significantly higher (85.0% vs. 80.7%, p < .001), whereas the accuracies of LI-RADS with TG-20% (81.3% vs. 80.7%, p = .404) and TG-30% (79.3% vs. 80.7%, p = .052) were not significant. The sensitivity of LI-RADS with TG-10% was higher than that of LI-RADS v2018 (79.0% vs. 72.5%, p < .001), whereas their specificities were not significantly different (96.6% vs. 96.6%, p > .999). CONCLUSION: TG-10% improved the sensitivity of LI-RADS by detecting additional hepatocellular carcinomas underestimated due to short-term follow-up. CLINICAL RELEVANCE STATEMENT: Threshold growth based on tumor growth rate can be clinically useful in the diagnosis of hepatocellular carcinoma, by improving the sensitivity of LI-RADS. KEY POINTS: • The diagnostic accuracy of Liver Imaging Reporting and Data System (LI-RADS) v2018 was not significantly affected by the time interval between prior and index assessments of threshold growth. • In the 334 hepatocellular carcinomas, the frequency of threshold growth was significantly higher using tumor growth rate ≥ 10%/month (TG-10%) than original threshold growth (53.3% vs. 18.0%, p < .001). • Compared with LI-RADS v2018 with the original threshold growth, LI-RADS with TG-10% had significantly higher accuracy (85.0% vs. 80.7%, p < .001) and sensitivity (79.0% vs. 72.5%, p < .001) but a similar specificity (96.6% vs. 96.6%, p > .999).

Feeding artery: a valuable feature for differentiation of regenerative nodule, dysplastic nodules and small hepatocellular carcinoma in CEUS LI-RADS.

OBJECTIVE: To investigate whether the feeding artery (FA) feature can aid in discriminating small hepatocellular carcinoma (HCC) using the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) from precancerous lesions. METHODS: Between June 2017 and May 2021, a total of 347 patients with 351 precancerous liver lesions or small HCCs who underwent CEUS were enrolled. Two independent radiologists assigned LI-RADS categories to all lesions and assessed the presence of the FA feature, which was used as an ancillary feature to either upgrade or downgrade the LI-RADS category. The diagnostic performance of CEUS LI-RADS, both with and without the FA feature, was evaluated based on accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: The FA feature was found to be more prevalent in HCC (85.54%, p < 0.001) than in regenerative nodules (RNs, 29.73%), low-grade dysplastic nodules (LGDNs, 33.33%), and high-grade dysplastic nodules (HGDNs, 55.26%). Furthermore, the presence of arterial phase hyperenhancement (APHE), washout (WO), and FA in liver nodules was associated with a higher expression of GPC-3 and Ki-67 compared to the group without these features (p < 0.001). After adjusting, the sensitivity and accuracy of LR-5 for HCC improved from 68.67% (95%CI: 62.46%, 74.30%) to 77.51% (95%CI: 71.72%, 82.44%) and from 69.23% (95%CI: 64.11%, 74.02%) to 73.79% (95%CI: 68.86%, 78.31%), respectively. CONCLUSION: The FA feature is a valuable feature for distinguishing small HCC and precancerous lesions and could be added as a possible ancillary feature in CEUS LI-RADS which was backed up by biomarkers. CLINICAL RELEVANCE STATEMENT: The presence of a feeding artery is a valuable imaging feature in the differentiation of HCC and precancerous lesions. Incorporating this characteristic in the CEUS LI-RADS can enhance the diagnostic ability. KEY POINTS: • Feeding artery is more frequent in HCC than in regenerative nodules, low-grade dysplastic nodules, and high-grade dysplastic nodules. • Feeding artery feature is a valuable ancillary feature for CEUS LI-RADS to differentiate regenerative nodules, low-grade dysplastic nodules, high-grade dysplastic nodules, and HCC. • The existence of feeding artery, arterial phase hyperenhancement, and washout is associated with more GPC-3 positive expression and higher Ki-67 expression than the group without these features.

Prognostic Role of the Progression of Late Gadolinium Enhancement in Hypertrophic Cardiomyopathy.

In hypertrophic cardiomyopathy (HCM), late gadolinium enhancement (LGE) extent ≥15% of left ventricular mass is considered a prognostic risk factor. LGE extent increases over time and the clinical role of the progression of LGE over time (LGE rate) was not prospectively evaluated. We sought to evaluate the prognostic role of the LGE rate in HCM. We enrolled 105 patients with HCM who underwent cardiac magnetic resonance (CMR) at baseline (CMR-I) and after ≥2 years of follow-up (CMR-II). LGE rate was defined as the ratio between the increase of LGE extent (grams) and the time interval (months) between examinations. A combined end point of sudden cardiac death, resuscitated cardiac arrest, appropriate Implanted Cardioverter Defibrillator (ICD) intervention, and sustained ventricular tachycardia was used (hard events). The percentage of patients with LGE extent ≥15% increased from 9% to 20% from CMR-I to CMR-II (p = 0.03). During a median follow-up of 52 months, 25 hard events were recorded. The presence of LGE ≥15% at CMR-II allowed a significant reclassification of the risk of patients than at LGE ≥15% at CMR-I (net reclassification improvement 0.21, p = 0.046). On the MaxStat analysis, the optimal prognostic cut point for LGE rate was >0.07 g/month. On the Kaplan-Meier curve, patients with LGE rate >0.07 had worse prognosis than those without (p <0.0001). LGE rate >0.07 allowed a significant reclassification of the risk compared with LGE ≥15% at CMR-I and at CMR-II (net reclassification improvement 0.49, p = 0.003). In the multivariable models, LGE rate >0.07 was the best independent predictor of hard events. In conclusion, CMR should be repeated after 2 years to reclassify the risk for sudden death of those patients. A high LGE rate may be considered a novel prognostic factor in HCM.

Diagnostic algorithm for subcentimeter hepatocellular carcinoma using alpha-fetoprotein and imaging features on gadoxetic acid-enhanced MRI.

OBJECTIVE: To investigate the role of serum alpha-fetoprotein (AFP) in diagnosing subcentimeter hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI (EOB-MRI). METHODS: This study retrospectively enrolled treatment-naïve patients with chronic hepatitis B who had a solitary subcentimeter observation on EOB-MRI from January 2017 to March 2023. Final diagnosis was confirmed by pathology for HCC and pathology or follow-up for benign controls. The AFP cutoff value for HCC was determined using Youden's index. Diagnostic criteria were developed according to significant findings in logistic regression analyses based on AFP and imaging features. The diagnostic performance of possible criteria was compared to the diagnostic hallmarks of HCC (arterial-phase hyperintensity and portal-phase hypointensity). RESULTS: A total of 305 patients (mean age, 51.5 ± 10.7 years; 153 men) were divided into derivation and temporal validation cohorts. Four findings, namely AFP >13.7 ng/mL, arterial-phase hyperintensity, portal-phase hypointensity, and transitional-phase hypointensity, were predictors of HCC. A new criterion (at least three of the four findings) showed higher sensitivity than the diagnostic hallmarks (derivation cohort, 71.6% vs. 52.3%, p < 0.001; validation cohort, 75.0% vs. 47.5%, p = 0.003) without decreasing specificity (derivation cohort, 92.5% vs. 92.5%, p > 0.999; validation cohort, 92.0% vs. 92.0%, p > 0.999). Another criterion (all four findings) achieved a slightly higher specificity than the diagnostic hallmark (derivation cohort, 99.1% vs. 92.5%, p = 0.023; validation cohort, 100.0% vs. 92.0%, p = 0.134). Subgroup analysis for hepatobiliary hypointense observations yielded similar results. CONCLUSION: Including AFP in the diagnostic algorithm may improve the diagnostic performance for subcentimeter HCC. CLINICAL RELEVANCE STATEMENT: Combining imaging features on gadoxetic acid-enhanced MRI with alpha-fetoprotein may enhance the diagnostic performance for subcentimeter HCC in treatment-naïve patients with chronic hepatitis B. KEY POINTS: • The traditional diagnostic hallmark of HCC (arterial-phase hyperintensity and portal-phase hypointensity) shows modest diagnostic performance for subcentimeter HCC on EOB-MRI. • Serum alpha-fetoprotein > 13.7 ng/mL, arterial-phase hyperintensity, portal-phase hypointensity, and transitional-phase hypointensity were independent predictors for subcentimeter HCC. • A criterion of at least three of the four above findings achieved a higher sensitivity without decreasing specificity.

Expression of GRP78 and its copartners in HEK293 and pancreatic cancer cell lines (BxPC-3/PANC-1) exposed to MRI and CT contrast agents.

Endoplasmic reticulum (ER) stress-associated chaperones trigger a defense mechanism called as unfolded protein response (UPR) which can manage apoptosis and be determinative in cell fate. Both anticancer drug effects and potential toxicity effects of magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were aimed to be evaluated. For this purpose, we investigated expression profiles of endoplasmic reticulum stress-associated chaperone molecules in human pancreatic tumor lines BxPC-3 and PANC-1 and control human embryonic kidney cells 293 (HEK293) induced with a variety of gadolinium and iohexol contrast agents. Protein expression levels of ER stress-associated chaperones (master regulator: GRP78/Bip and its copartners: Calnexin, Ero1, PDI, CHOP, IRE1α and PERK) were evaluated with Western blotting. Expression levels at mRNA level were also assessed for GRP78/Bip and CHOP with real-time PCR. Induction of cells was carried out with four different Gd-based contrast agents (GBCAs): (Dotarem, Optimark, Primovist and Gadovist) and two different iohexol agents (Omnipol, Omnipaque). CT contrast agents tested in the study did not result in significant ER stress in HEK293 cells. However, they do not seem to have theranostic potential in pancreas cancer through ER pathway. The potential efficiency of macrocyclic MRI contrast agents to provoke apoptosis via ER stress-associated chaperones in BxPC-3 cells lends credibility for their future theranostic use in pancreas cancer as long as undesired toxicity effects were carefully considered. ER stress markers and/or contrast agents seem to have promising potential to be translated into the clinical practice to manage pancreas cancer progression.

Effect of late gadolinium enhancement on left atrial impairment in myocarditis patients.

OBJECTIVE: The aims of our study were to investigate the effect of the extent and location of late gadolinium enhancement (LGE) on the left atrium (LA) function in patients with acute myocarditis (AM) using cardiovascular magnetic resonance (CMR). METHOD: This retrospective study performed CMR scans in 113 consecutive patients (89 males, 24 females; mean age 45.8 ± 17.3 years) with AM that met the updated Lake Louise criteria. Reservoir, conduit, and booster LA functions were analyzed by CMR feature tracking using dedicated software. Besides LA strain measurements, myocardial scar location and extent were assigned and quantified by LGE imaging. RESULTS: AM patients with septal LGE had impaired reservoir, conduit, and conduit strain rate function in comparison with AM patients with non-septal LGE (p = 0.001, for all). In fully adjusted multivariable linear regression, reservoir and conduit were significantly associated with left ventricle (LV) LGE location (ß coefficient = 8.205, p = 0.007; ß coefficient = 5.185, p = 0.026; respectively). In addition, LA parameters decreased according to the increase in the extent of LV fibrosis (LGE ≤ 10%; LGE 11-19%; LGE ≥ 20%). After adjustment in multivariable linear regression, the association with LV LGE extent was no longer statistically significant. CONCLUSION: In patients with acute myocarditis, LA function abnormalities are significantly associated with LV LGE location, but not with LGE extent. Septal LGE is paralleled by a deterioration of LA reservoir and conduit function. CLINICAL RELEVANCE STATEMENT: Left atrium dysfunction is associated with the presence of late gadolinium enhancement in the left ventricle septum and can be useful in the clinical prognostication of patients with acute myocarditis, allowing individually tailored treatment. KEY POINTS: • Myocardial fibrosis is related to atrial impairment. • The location of myocardial fibrosis is the main determinant of atrial dysfunction in myocarditis patients. • The quantification of atrial mechanisms may provide more in-depth insight into myocarditis pathophysiology.

Suboptimal performance of LI-RADS v2018 on gadoxetic acid-enhanced MRI for detecting hepatocellular carcinoma in liver transplant candidates.

OBJECTIVES: To evaluate the diagnostic performance for hepatocellular carcinoma (HCC) detection of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 on gadoxetic acid-enhanced MRI, comparing liver transplant candidates (LT group) with patients who underwent surgical resection (SR group), and to determine significant clinical factors for diagnostic performance of LI-RADS v2018. METHODS: Patients who underwent gadoxetic acid-enhanced MRI and subsequent SR or LT for HCC were retrospectively included between January 2019 and December 2020. The sensitivity and specificity of LI-RADS LR-5 for HCC were compared between the two groups using generalized estimating equations. The accuracy of patient allocation according to the Milan criteria was calculated for the LT group. Univariable and multivariable logistic regression analyses were performed to determine significant clinical factors associated with the sensitivity of LI-RADS. RESULTS: Of the 281 patients, 237 were assigned to the SR group, and 44 were assigned to the LT group. The LT group showed significantly lower per-patient (48.5% vs. 79.6%, p < .001) and per-lesion sensitivity (31.0% vs. 75.9%, p < .001) than the SR group, whereas no significant difference in both per-patient (100.0% vs. 91.7%, p > .99) and per-lesion specificities (100.0% vs. 94.1%, p > .99). The accuracy of patient allocation was 50.0%. Sensitivity was significantly lower in patients with a smaller lesion size (p < .001), a larger lesion number (p = .002), and a higher Child-Pugh score (p = .009). CONCLUSION: LI-RADS v2018 on gadoxetic acid-enhanced MRI might be insufficient in liver transplant candidates and other diagnostic imaging tests should be considered in patients with these significant clinical factors. CLINICAL RELEVANCE STATEMENT: In liver transplant candidates with a smaller lesion size, a larger lesion number, and a higher Child-Pugh score, imaging tests other than gadoxetic acid-enhanced MRI may be clinically useful to determine the transplant eligibility. KEY POINTS: • The sensitivity of the Liver Imaging Reporting and Data System (LI-RADS) was lower in liver transplant candidates than in those who underwent surgical resection. • With the use of gadoxetic acid-enhanced MRI, the accuracy of patient allocation for liver transplantation on the basis of the Milan criteria was suboptimal. • The sensitivity of LI-RADS v2018 was significantly associated with lesion size, lesion number, and Child-Pugh classification.

Late gadolinium enhanced cardiac MR derived radiomics approach for predicting all-cause mortality in cardiac amyloidosis: a multicenter study.

OBJECTIVES: To evaluate the prognostic value of radiomics features based on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) images in patients with cardiac amyloidosis (CA). METHODS: This retrospective study included 120 CA patients undergoing CMR at three institutions. Radiomics features were extracted from global and three different segments (base, mid-ventricular, and apex) of left ventricular (LV) on short-axis LGE images. Primary endpoint was all-cause mortality. The predictive performance of the radiomics features and semi-quantitative and quantitative LGE parameters were compared by ROC. The AUC was used to observe whether Rad-score had an incremental value for clinical stage. The Kaplan-Meier curve was used to further stratify the risk of CA patients. RESULTS: During a median follow-up of 12.9 months, 30% (40/120) patients died. There was no significant difference in the predictive performance of the radiomics model in different LV sections in the validation set (AUCs of the global, basal, middle, and apical radiomics model were 0.75, 0.77, 0.76, and 0.77, respectively; all p > 0.05). The predictive performance of the Rad-score of the base-LV was better than that of the LGE total enhancement mass (AUC:0.77 vs. 0.54, p < 0.001) and LGE extent (AUC: 0.77 vs. 0.53, p = 0.004). Rad-score combined with Mayo stage had better predictive performance than Mayo stage alone (AUC: 0.86 vs. 0.81, p = 0.03). Rad-score (≥ 0.66) contributed to the risk stratification of all-cause mortality in CA. CONCLUSIONS: Compared to quantitative LGE parameters, radiomics can better predict all-cause mortality in CA, while the combination of radiomics and Mayo stage could provide higher predictive accuracy. CLINICAL RELEVANCE STATEMENT: Radiomics analysis provides incremental value and improved risk stratification for all-cause mortality in patients with cardiac amyloidosis. KEY POINTS: • Radiomics in LV-base was superior to LGE semi-quantitative and quantitative parameters for predicting all-cause mortality in CA. • Rad-score combined with Mayo stage had better predictive performance than Mayo stage alone or radiomics alone. • Rad-score ≥ 0.66 was associated with a significantly increased risk of all-cause mortality in CA patients.

Liver Imaging Reporting and Data System version 2018 category 5 for diagnosing hepatocellular carcinoma: an updated meta-analysis.

OBJECTIVE: We performed an updated meta-analysis to determine the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS, LR) 5 category for hepatocellular carcinoma (HCC) using LI-RADS version 2018 (v2018), and to evaluate differences by imaging modalities and type of MRI contrast material. METHODS: The MEDLINE and Embase databases were searched for studies reporting the performance of LR-5 using v2018 for diagnosing HCC. A bivariate random-effects model was used to calculate the pooled per-observation sensitivity and specificity. Subgroup analysis was performed based on imaging modalities and type of MRI contrast material. RESULTS: Forty-eight studies qualified for the meta-analysis, comprising 9031 patients, 10,547 observations, and 7216 HCCs. The pooled per-observation sensitivity and specificity of LR-5 for diagnosing HCC were 66% (95% CI, 61-70%) and 91% (95% CI, 89-93%), respectively. In the subgroup analysis, MRI with extracellular agent (ECA-MRI) showed significantly higher pooled sensitivity (77% [95% CI, 70-82%]) than CT (66% [95% CI, 58-73%]; p = 0.023) or MRI with gadoxetate (Gx-MRI) (65% [95% CI, 60-70%]; p = 0.001), but there was no significant difference between ECA-MRI and MRI with gadobenate (gadobenate-MRI) (73% [95% CI, 61-82%]; p = 0.495). Pooled specificities were 88% (95% CI, 80-93%) for CT, 92% (95% CI, 86-95%) for ECA-MRI, 93% (95% CI, 91-95%) for Gx-MRI, and 91% (95% CI, 84-95%) for gadobenate-MRI without significant differences (p = 0.084-0.803). CONCLUSIONS: LI-RADS v2018 LR-5 provides high specificity for HCC diagnosis regardless of modality or contrast material, while ECA-MRI showed higher sensitivity than CT or Gx-MRI. CLINICAL RELEVANCE STATEMENT: Refinement of the criteria for improving sensitivity while maintaining high specificity of LR-5 for HCC diagnosis may be an essential future direction. KEY POINTS: • The pooled per-observation sensitivity and specificity of LR-5 for diagnosing HCC using LI-RADSv2018 were 66% and 91%, respectively. • ECA-MRI showed higher sensitivity than CT (77% vs 66%, p = 0.023) or Gx-MRI (77% vs 65%, p = 0.001). • LI-RADS v2018 LR-5 provides high specificity (88-93%) for HCC diagnosis regardless of modality or contrast material type.

Localization of contrast-enhanced breast lesions in ultrafast screening MRI using deep convolutional neural networks.

OBJECTIVES: To develop a deep learning-based method for contrast-enhanced breast lesion detection in ultrafast screening MRI. MATERIALS AND METHODS: A total of 837 breast MRI exams of 488 consecutive patients were included. Lesion's location was independently annotated in the maximum intensity projection (MIP) image of the last time-resolved angiography with stochastic trajectories (TWIST) sequence for each individual breast, resulting in 265 lesions (190 benign, 75 malignant) in 163 breasts (133 women). YOLOv5 models were fine-tuned using training sets containing the same number of MIP images with and without lesions. A long short-term memory (LSTM) network was employed to help reduce false positive predictions. The integrated system was then evaluated on test sets containing enriched uninvolved breasts during cross-validation to mimic the performance in a screening scenario. RESULTS: In five-fold cross-validation, the YOLOv5x model showed a sensitivity of 0.95, 0.97, 0.98, and 0.99, with 0.125, 0.25, 0.5, and 1 false positive per breast, respectively. The LSTM network reduced 15.5% of the false positive prediction from the YOLO model, and the positive predictive value was increased from 0.22 to 0.25. CONCLUSIONS: A fine-tuned YOLOv5x model can detect breast lesions on ultrafast MRI with high sensitivity in a screening population, and the output of the model could be further refined by an LSTM network to reduce the amount of false positive predictions. CLINICAL RELEVANCE STATEMENT: The proposed integrated system would make the ultrafast MRI screening process more effective by assisting radiologists in prioritizing suspicious examinations and supporting the diagnostic workup. KEY POINTS: • Deep convolutional neural networks could be utilized to automatically pinpoint breast lesions in screening MRI with high sensitivity. • False positive predictions significantly increased when the detection models were tested on highly unbalanced test sets with more normal scans. • Dynamic enhancement patterns of breast lesions during contrast inflow learned by the long short-term memory networks helped to reduce false positive predictions.

Contrast-enhanced cardiac MRI is superior to non-contrast mapping to predict left ventricular remodeling at 6 months after acute myocardial infarction.

OBJECTIVES: Parametric mapping constitutes a novel cardiac magnetic resonance (CMR) technique enabling quantitative assessment of pathologic alterations of left ventricular (LV) myocardium. This study aimed to investigate the clinical utility of mapping techniques with and without contrast agent compared to standard CMR to predict adverse LV remodeling following acute myocardial infarction (AMI). MATERIALS AND METHODS: A post hoc analysis was performed on sixty-four consecutively enrolled patients (57 ± 12 years, 54 men) with first-time reperfused AMI. Baseline CMR was obtained at 8 ± 5 days post-AMI, and follow-up CMR at 6 ± 1.4 months. T1/T2 mapping, T2-weighted, and late gadolinium enhancement (LGE) acquisitions were performed at baseline and cine imaging was used to determine adverse LV remodeling, defined as end-diastolic volume increase by 20% at 6 months. RESULTS: A total of 11 (17%) patients developed adverse LV remodeling. At baseline, patients with LV remodeling showed larger edema (30 ± 11 vs. 22 ± 10%LV; p < 0.05), infarct size (24 ± 11 vs. 14 ± 8%LV; p < 0.001), extracellular volume (ECVinfarct; 63 ± 12 vs. 47 ± 11%; p < 0.001), and native T2infarct (95 ± 16 vs. 78 ± 17 ms; p < 0.01). ECVinfarct and infarct size by LGE were the best predictors of LV remodeling with areas under the curve (AUCs) of 0.843 and 0.789, respectively (all p < 0.01). Native T1infarct had the lowest AUC of 0.549 (p = 0.668) and was inferior to edema size by T2-weighted imaging (AUC = 0.720; p < 0.05) and native T2infarct (AUC = 0.766; p < 0.01). CONCLUSION: In this study, ECVinfarct and infarct size by LGE were the best predictors for the development of LV remodeling within 6 months after AMI, with a better discriminative performance than non-contrast mapping CMR. CLINICAL RELEVANCE STATEMENT: This study demonstrates the predictive value of contrast-enhanced and non-contrast as well as conventional and novel CMR techniques for the development of LV remodeling following AMI, which might help define precise CMR endpoints in experimental and clinical myocardial infarction trials. KEY POINTS: • Multiparametric CMR provides insights into left ventricular remodeling at 6 months following an acute myocardial infarction. • Extracellular volume fraction and infarct size are the best predictors for adverse left ventricular remodeling. • Contrast-enhanced T1 mapping has a better predictive performance than non-contrast standard CMR and T1/T2 mapping.

Quantitative information from gadobenate dimeglumine-enhanced MRI can predict proliferative subtype of solitary hepatocellular carcinoma: a multicenter retrospective study.

OBJECTIVES: To investigate the value of quantitative parameters derived from gadobenate dimeglumine-enhanced magnetic resonance imaging (MRI) for predicting molecular subtype of hepatocellular carcinoma (HCC) and overall survival. METHODS: This multicenter retrospective study included 218 solitary HCC patients who underwent gadobenate dimeglumine-enhanced MRI. All HCC lesions were resected and pathologically confirmed. The lesion-to-liver contrast enhancement ratio (LLCER) and lesion-to-liver contrast (LLC) were measured in the hepatobiliary phase. Potential risk factors for proliferative HCC were assessed by logistic regression. The ability of LLCER and LLC to predict proliferative HCC was assessed by the receiver operating characteristic (ROC) curve. Prognostic factors were evaluated using the Cox proportional hazards regression model for survival outcomes. RESULTS: LLCER was an independent predictor of proliferative HCC (odds ratio, 0.015; 95% confidence interval [CI], 0.008-0.022; p < 0.001). The area under the ROC curve was 0.812 (95% CI, 0.748-0.877), higher than that of LLC, alpha-fetoprotein > 100 ng/ml, satellite nodules, and rim arterial phase hyperenhancement (all p ≤ 0.001). HCC patients with LLCER < -4.59% had a significantly higher incidence of proliferative HCC than those with the LLCER ≥ -4.59%. During the follow-up period, LLCER was an independent predictor of overall survival (hazard ratio, 0.070; 95% CI, 0.015-0.324; p = 0.001) in HCC patients. CONCLUSIONS: Gadobenate dimeglumine-enhanced quantitative parameter in the hepatobiliary phase can predict the proliferative subtype of solitary HCC with a moderately high accuracy. CLINICAL RELEVANCE STATEMENT: Quantitative information from gadobenate dimeglumine-enhanced MRI can provide crucial information on hepatocellular carcinoma subtypes. It might be valuable to design novel therapeutic strategies, such as targeted therapies or immunotherapy. KEY POINTS: • The lesion-to-liver contrast enhancement ratio (LLCER) is an independent predictor of proliferative hepatocellular carcinoma (HCC). • The ability of LLCER to predict proliferative HCC outperformed lesion-to-liver contrast, alpha-fetoprotein > 100 ng/ml, satellite nodules, and rim arterial phase hyperenhancement. • HCC patients with LLCER < -4.59% had a significantly higher incidence of proliferative HCC than those with the LLCER ≥ -4.59%.

Absence of visible infarction on cardiac magnetic resonance imaging despite the established diagnosis of myocardial infarction by 4th Universal Definition of Myocardial Infarction.

AIMS: Myocardial scarring due to acute myocardial infarction (AMI) can be visualized by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. However, a recent study revealed a group of Type 1 AMI patients with undetectable myocardial injury on LGE. This study aims to describe these cases in detail and explore possible explanations for this new phenomenon. METHODS AND RESULTS: A total of 137 patients diagnosed with either ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (non-STEMI) diagnosed according to the 4th Universal Definition of Myocardial Infarction underwent LGE-CMR after invasive coronary angiography. Fourteen of them (10.2%) showed no LGE and were included in the final study population. Most patients presented with acute chest pain, 3 patients were diagnosed as STEMI, and 11 as non-STEMI. Peak high-sensitive cardiac troponin T ranged from 45 to 1173 ng/L. A culprit lesion was identified in 12 patients. Severe coronary stenoses were found in five patients, while seven patients had subtotal to total coronary artery occlusion. Percutaneous coronary intervention was performed in 10 patients, while 2 patients required coronary artery bypass grafting and no intervention was required in 2 patients. Cardiac magnetic resonance was performed 30 (4-140) days after the initial presentation. Most patients showed preserved left ventricular ejection fraction on CMR. No alternative reasons for the rise/fall of high-sensitive cardiac troponin T were found. CONCLUSION: The absence of LGE on CMR in patients with Type 1 AMI is a new finding. While insufficient spatial resolution of LGE imaging, delayed CMR performance, spontaneous reperfusion, and coronary collaterals may provide some explanations, further investigations are required to fully understand this phenomenon.

Evaluation of gadolinium-based contrast agents in juvenile CD-1 mice including behavioral evaluations.

INTRODUCTION: Seven gadolinium-based contrast agents (GBCAs), four linear and three macrocyclic, were evaluated for potential effects on development, including behavior of juvenile CD-1 mice. METHODS: The GBCAs were administered via intravenous injection once daily on postnatal day (PND) 9, 12, 15, 18, and 21 (PND 1 was the day of delivery) at doses up to twice the human equivalent clinical dose (i.e., 0.63 mmol Gd/kg for gadoxetate disodium and 2.5 mmol Gd/kg for the other GBCAs). Mice were bled for evaluation of exposure (plasma) to gadolinium (Gd) on PND 9, 12, and 70. At scheduled euthanasia, the liver, spleen, brain, skin (dorsal surface), bone (left femur), and kidneys were excised from up to six mice/sex/group on PND 10, 22, or 70 for the determination of Gd levels and histopathological analysis. All mice were monitored for toxicity, growth and survival, sexual maturation, and behavior. CONCLUSION: Gd was quantifiable in the brain tissues with levels declining over time. There was no long-term effect on the growth and development for mice exposed to any of the GBCAs. There was no impact on neurodevelopment as assessed by brain histology and validated neurobehavioral tests, including a functional observational battery, motor activity, and learning and memory as evaluated in the Morris water maze. For all GBCAs, the highest dose tested represented the no-observable-adverse-effect level in juvenile mice.

MVI-Wise GAN: Synthetic MRI to Improve Microvascular Invasion Prediction in Hepatocellular Carcinoma.

MRI is crucial for the diagnosis of HCC patients, especially when combined with CT images for MVI prediction, richer complementary information can be learned. Many studies have shown that whether hepatocellular carcinoma is accompanied by vascular invasion can be evidenced by imaging examinations such as CT or MR, so they can be used as a multimodal joint prediction to improve the prediction accuracy of MVI. However, it is high-risk, time-consuming and expensive in current clinical diagnosis due to the use of gadolinium-based contrast agent (CA) injection. If MRI could be synthesized without CA injection, there is no doubt that it would greatly optimize the diagnosis. Based on this, this paper proposes a high-quality image synthesis network, MVI-Wise GAN, that can be used to improve the prediction of microvascular invasion in HCC. It starts from the underlying imaging perspective, introduces K-space and feature-level constraints, and combines three related networks (an attention-aware generator, a convolutional neural network-based discriminator and a region-based convolutional neural network detector) Together, precise tumor region detection by synthetic tumor-specific MRI. Accurate MRI synthesis is achieved through backpropagation, the feature representation and context learning of HCC MVI are enhanced, and the performance of loss convergence is improved through residual learning. The model was tested on a dataset of 256 subjects from Run Run Shaw Hospital of Zhejiang University. Experimental results and quantitative evaluation show that MVI-Wise GAN achieves high-quality MRI synthesis with a tumor detection accuracy of 92.3%, which is helpful for the clinical diagnosis of liver tumor MVI.