Investigative Radiology最新文献

Background: 7T MRI received FDA/CE clearance almost 7 years ago. However, until today, it has not yet been widely adopted in clinical routine. This is mainly due to field inhomogeneities that impede whole-brain coverage. Moreover, the long scan times often associated with high-resolution imaging are an additional limiting factor.

Purpose: To combine calibration-free parallel transmit technology (pTx) using universal pulses (UP) with advanced imaging acceleration strategies to achieve homogenous multicontrast 7T MRI with whole-brain coverage and high spatial resolution in short scan time.

Materials and methods: Ten healthy volunteers were scanned both with conventional vendor-provided sequences and with custom sequences for anatomical whole-brain imaging [-weighted, -weighted, FLAIR, and susceptibility-weighted]. The scan times for the 2 anatomical protocols were matched (25 minutes). In addition, a quantitative MRI protocol [multi-parametric mapping (MPM) and chemical exchange saturation transfer (CEST)] was scanned twice using custom sequences with conventional (circular polarized) and UPs, respectively, in a scan time of 2×25 minutes. Moreover, 4 patients with different neurological diseases were scanned, namely temporal lobe epilepsy, spinocerebellar ataxia, cerebral amyloid angiopathy, and glioblastoma. For the patients, only optimized custom sequences with UPs were acquired.

Results: Compared with conventional implementations, the custom sequences provide strongly improved image homogeneity and quality with significantly higher SNR and CNR across the whole brain, including cerebellum and brain stem. Moreover, UPs improve the repeatability of derived quantitative parameters. The suggested protocol has additionally been successfully demonstrated in 4 patients with different neurological pathologies.

Conclusions: Homogeneous whole-brain 7T MRI with high spatial resolution and high image quality is possible in clinically feasible scan times. The developed protocol can be applied without any expert knowledge and is ready for clinical use. The approach could largely extend applicability of UHF MRI in neuroradiology paving the way for increased routine use of 7T MRI.

Objectives: This study aims to improve the radiopacity of absorbable bone cements through the addition of gadolinium nanoparticles (GdNP). We also aim to determine whether photon-counting CT (PCCT) provides superior contrast-to-noise ratio (CNR) between GdNP-loaded bone cement and vertebral bone when compared with energy-integrating CT (EID-CT), and to evaluate the accuracy of PCCT material decomposition for quantifying gadolinium concentration in solution and the GdNP-loaded cements.

Materials and methods: GdNPs were synthesized using a one-pot thermal decomposition method and characterized using transmission electron microscopy and dynamic light scattering. Hydroxyapatite-based bone cement was loaded with varying mass fractions of GdNPs (0% to 10% w/w), and the CNR between the GdNP-loaded cement and vertebral bone was evaluated using preclinical micro-EID-CT and micro-PCCT scanners. Gadolinium material decomposition images were used to measure the amount of gadolinium present in each of the cements. In addition, gadolinium standards (0 to 20 mg/mL) were imaged with a preclinical micro-PCCT, and the concentration of gadolinium in the vials was estimated using gadolinium material decomposition images.

Results: The synthesized GdNPs had a mean diameter of 15.42±1.82 nm. Signal intensity increased with increasing mass fractions of GdNPs for both EID-CT and PCCT. In EID-CT images, cements with ≥4% GdNP loading had higher CNRs relative to bone than the cement with no GdNP loading (P<0.05). The CNR between the 8% and 10% GdNP-loaded bone cement significantly differed from than the bone cement with no GdNP loading for all PCCT energy bins (P<0.05). The 42-51 keV energy bin yielded the largest CNRs overall when compared with the CNRs of other energy bins. Overall, the CNRs obtained from PCCT images were larger than the EID-CT CNRs. The concentration of gadolinium in the cements measured using the PCCT material decomposition images was correlated with the mass fractions of GdNP (r=0.9753). Estimated gadolinium concentrations were highly correlated with the nominal concentration of the gadolinium standards (r=0.999) and the PCCT was able to accurately quantify gadolinium concentrations with a root mean square error of 1.60 mg/mL.

Conclusions: The use of GdNPs led to a higher cement-vertebra CNR for both EID-CT and PCCT. Overall, PCCT demonstrated higher CNRs than EID-CT. Material decomposition successfully quantified the concentration of gadolinium in vials and allowed for improved visual differentiation of the GdNP-loaded bone cement from the calcium-based vertebral bodies. Thus, the incorporation of radiopaque GdNPs and imaging with PCCT improved visualization of the bone cement. These methods could be used to improve monitoring of implanted bone cements. In addition, PCCT material decomposition enabled accurate quantification of gadolinium in solution.

Objectives: Previous studies in rodents have investigated the potential effects of gadolinium-based contrast agents (GBCAs) on the peripheral nervous system; this study aimed to assess the potential effects of 2 GBCAs on the peripheral nervous system of non-human primates (NHPs) and to evaluate their toxicokinetic profile.

Materials and methods: Eighteen cynomolgus monkeys ( Macaca fascicularis ; 2 to 4 years old, Mauritian origin) of both sexes (3 animals/group/sex) were intravenously administered once with either gadobenate dimeglumine or gadoteridol at 0.3 mmol/kg, or with saline (0.6 mL/kg). This was followed by a 52-week recovery phase. Safety assessments were based on clinical observations, body weights, neurobehavioral observations, electrophysiologic nerve conduction tests, nerve assessment in skin biopsies (pre-dose and at weeks 2, 17, and 51), and clinical pathology evaluation. Blood for toxicokinetic evaluations was collected at pre-dose and at 5 minutes and at 1, 4, 7, and 24 hours post-dose.

Results: No GBCA-related changes were noted from clinical and neurobehavioral observation. All sensory and motor nerve conduction metrics remained within a normal, physiologically functional range at all time points for all animals. Hematoxylin and eosin-stained sections revealed no induced changes in epidermal and subepidermal tissues. Image analysis did not reveal histomorphometrical differences between control and GBCA-treated animals. Systemic exposure to gadolinium (Gd) was comparable between sexes and was consistent after the administration of the 2 GBCAs; mean Gd half-life values, based on data from 5 minutes to 24 hours post-dose, were about 3.5 hours for gadobenate dimeglumine and about 3 hours for gadoteridol. For both GBCAs, systemic clearance was rapid at ∼0.16 L/h/kg, with a distribution volume ranging from 0.13 to 0.17 L/kg, indicating extracellular space distribution.

Conclusion: A single intravenous administration of 0.3 mmol/kg gadobenate dimeglumine or gadoteridol in NHPs was well tolerated and did not induce effects on the peripheral nervous system.

Background: The current standard dose of extracellular, multipurpose gadolinium-based contrast agents (GBCAs) of 0.1 mmol Gd/kg body weight (bw) was first suggested in 1984, 40 years ago. Although the safety and efficacy of both higher and lower doses ("non-standard dosing") have been extensively investigated over the years, the recent introduction of high-relaxivity macrocyclic GBCAs provides, for the first time, a viable lower-dose alternative.

Objective: To systematically explore published rationales for nonstandard dosing of GBCAs and discuss the potential future impact of high-relaxivity contrast agents.

Materials and methods: A systematic literature review was conducted using Embase and MEDLINE/PubMED, covering studies published from 1991 to 2024. Publications were categorized by clinical indication, administered GBCA dose, study design, and rationale for nonstandard dosing. The dose of 0.1 mmol Gd/kg body weight was defined as the "standard" reference for comparison.

Results: Eighty-seven publications comparing different nonstandard dosing regimens with the standard dose were finally selected, which included 43 high-dose and 58 low-dose studies. The rationales for using high-dose administration were to achieve better contrast (25/43; 58%) and to improve lesion detection (15/43; 35%). These high-dose studies were performed primarily in the CNS until 2006. Twenty-nine studies (29/43; 67%) reported improved outcomes compared with standard dose, and 1 study (1/43; 2%) reported comparable outcomes. Rationales for using low-dose administration were related to (1) NSF (31/58; 53%); (2) Gd exposure (23/58; 40%); (3) cost (22/58; 38%); (4) unspecified safety (22/58; 38%); (5) Gd retention/presence (19/58; 33%); and (6) the environment (7/58; 12%). From 1991 to 2006, cost was the primary rationale for lower dose administration. From 2008, NSF was noted, from 2017 onward, Gd retention/presence emerged as an identified rationale, and most recently, to minimize environmental impact. Forty-nine of 58 (84%) investigating low-dose regimens reported comparable outcomes, 7 studies (12%) reported inferior outcomes compared with standard dose. However, 36 of the 49 low-dose studies reporting comparable outcomes modified not only the dose but additionally other parameters, or they applied a study design potentially impacting study strength. To reliably allow for a substantially lower dose across a broad range of indications, the next generation of high-relaxivity low-dose GBCAs (gadopiclenol, gadoquatrane) was developed.

Conclusions: For over 34 years, there has been a consistent demand to lower GBCA doses, with an increasing number of rationales over time. The high-relaxivity, low-dose mGBCAs show promise for reducing Gd dose while maintaining high image quality, potentially defining a new standard dose.

Background: Blooming artifacts from calcified plaques can obscure the vessel lumen, leading to overestimation of stenosis severity. Spectral coronary angiography with photon-counting detector CT (PCD-CT) provides virtual monoenergetic images (VMIs) for coronary artery disease assessment. While VMIs at high VMI energy levels reduce calcium blooming, iodine contrast is diminished, limiting diagnostic value. This study evaluated whether contrast media with an atomic number higher than iodine (high-Z) preserve vascular contrast using high VMI energy levels, thereby improving the accuracy of stenosis quantification.

Methods: A phantom with 4 and 6 mm diameter rods to mimic small diameter vessels containing eccentric calcified plaques causing 25%, 50%, and 75% diameter stenoses was scanned with a dual-source PCD-CT system. Five different contrast media, including iodine, tungsten, holmium, hafnium, and bismuth, were tested. VMIs were reconstructed from 40 to 190 keV in 1-keV steps. Vessel attenuation, contrast-to-noise ratio (CNR), and stenoses were measured. Qualitative assessment of image quality was performed.

Results: Iodine attenuation was high at lower VMI energy levels and dropped below 250 HU at >100 keV. Tungsten, holmium, hafnium, and bismuth maintained >250 HU attenuation throughout the entire energy range. Vessel CNR of iodine was high at lower and decreased at higher VMI energy levels, similar to the CNR of holmium and bismuth, though to a lesser extent. In distinction, CNRs of tungsten and hafnium were lower at lower VMI energy levels and increased to a relatively constant level at higher keV. Tungsten CNR increased with energy, approaching ~40 at high keV. Across all contrast media and stenosis degrees, stenoses were overestimated on low VMI energy levels (24% to 32.5% at 40 keV), while the degree of overestimation decreased at higher VMI energy levels (0% to 13.5% at 190 keV). At 190 keV, tungsten, hafnium, and bismuth showed ≤2.5% stenosis overestimation, compared with iodine (10% to 13.5%). Image quality varied between contrast media and energy levels: new very high-Z contrast media achieved higher scores, while iodine peaked at lower keV (55 to 70 keV) and, due to loss of contrast at higher energies, received the lowest overall scores.

Conclusions: As compared with iodine, very high-Z contrast media enable superior lumen definition and more accurate stenosis assessment, also at high VMI energy levels, which minimize calcium blooming.

Abstract: Gadopiclenol was initially developed as a high-relaxivity, nonspecific magnetic resonance imaging contrast agent to enhance image quality and thereby improve diagnostics. This design required a highly demanding Drug Target Profile, addressing not only relaxivity but also factors such as physicochemical properties of the injectable solution (viscosity, osmolality, heat sterilization compatibility), pharmacokinetics and toxicity, particularly related to the stability of the complex. These considerations led to a multiparametric molecular design based on a gadolinium complex characterized by the following features: (1) a macrocyclic, nonionic structure based on the PCTA framework with 2 water molecules in the inner sphere; (2) the introduction of steric constraints around the gadolinium to enhance stability and reduce relaxivity quenching by endogenous ions; (3) slowed rotational diffusion due to gadolinium's position at the center of the complex; and (4) the incorporation of 3 hydrophilic amino polyol pendant arms to ensure aqueous solubility, reduce binding with endogenous proteins, and enhance product safety.This rational design led to the creation of a first prototype, P03277V1. However, the occurrence of nephrogenic systemic fibrosis necessitated modifications to the Drug Target Profile, aimed at improving the complex's stability and reducing production costs. This was achieved through the discovery of an isomerization process for P03277V1, resulting in gadopiclenol, which demonstrated excellent kinetic stability.The rational design of gadopiclenol thus exemplifies the concept of Property-Based Drug Design used in medicinal chemistry. It also highlights that the complexity of designing a diagnostic agent is comparable to that of a therapeutic agent. Furthermore, the case of gadopiclenol illustrates that the medical positioning of a drug candidate can evolve during clinical development. Gadopiclenol's medical positioning shifted from being a product with high relaxivity to improve signal strength, to one intended for use at a half dose to limit gadolinium injection and minimize risks to patients, such as nephrogenic systemic fibrosis or accumulation in specific areas of the brain. Currently, gadopiclenol is approved for clinical use at a dose of 0.05 mmol/kg to minimize gadolinium exposure to patients. Whether the 0.1 mmol/kg dose can be used to enhance clinical diagnostics and improve patient management in the future remains to be seen.

Objectives: To develop a simple rule-of-thumb on how to reduce the contrast medium (CM) dose in photon-counting detector CT (PCD-CT) when lowering the energy of the reconstructed virtual mono-energetic images (VMI) while maintaining the contrast-to-noise ratio (CNR) for parenchymal CT and CTA.

Materials and methods: Spectral abdominal and chest CT phantoms were scanned using a portal venous phase (PVP) abdominal and a high-pitch CTA protocol, respectively, on a first-generation dual-source PCD-CT. The phantoms contained cylindrical rods with iodine in water equivalent material (0.5/1.0/2.0/5.0/10.0/15.0 mg I/mL) and ICRU muscle tissue. The phantoms were complemented with 2 fat equivalent rings to mimic different patient sizes. Iodine contrast, image noise, noise power spectra (NPS), and iodine CNR were investigated in VMIs with different energies (40 to 60 keV in steps of 5 keV). This was done for different iodine concentrations, phantom sizes, x-ray tube voltages (120 kV and 140 kV) and radiation doses. In addition, 15 abdominal and 15 CT angiographic patient scans [body mass index (BMI) range: 17 to 37 kg/m2] were retrospectively analyzed to determine the CNR at different VMI energies.

Results: Contrast at a given iodine concentration and VMI energy was independent of phantom size, radiation dose, and acquisition voltage (kV). With decreasing VMI energy, the maximum of the NPS curves increased, while their shape remained similar, indicating higher noise but similar noise texture. The CNR increased with lower VMI energy for a given iodine concentration and phantom size, while CNR decreased with increasing phantom size for a given VMI energy and iodine concentration. When the VMI energy was lowered by 5 keV steps in the range of 60 to 40 keV, similar CNR could be maintained when reducing the iodine concentration at each step by 11.7% to 13.7% for abdominal PVP scans and 11.8% to 14.5% for CTAs. CNR analysis of the patient scans confirmed these findings: a 5 keV reduction in VMI energy led to a mean±SD 11.4%±0.4% and 13.7%±1.0% increase in CNR for abdomen PVP and CTA scans, respectively. This can be translated to a corresponding reduction in CM dose when a constant CNR is aimed for. From these results, a simple, robust rule-of-thumb was derived, the 10-to-5 rule: For the evaluated PCD-CT protocols, CNR can be maintained with about 10% less CM dose for each reduction of the VMI energy by 5 keV.

Conclusions: This phantom study, which was complemented with a retrospective proof-of-principle patient study, showed that a simple, easy to implement 10-to-5 rule-of-thumb might be used in daily practice for contrast-enhanced PCD-CT. It allows for individual adaptation of the CM dose to the VMI energy applied.

Objectives: Accurate detection and quantification of liver iron overload (LIO) in patients with thalassemia is crucial for guiding iron chelation therapy and preventing iron-related organ damage. While conventional multiecho gradient-echo (GRE) based MR at 1.5T is the clinical standard, with increasing availability of 3.0T systems, clinically reliable alternatives are needed. The ultra-short echo time (UTE) MRI sequence may offer improved assessment of LIO on 3.0T. The objective of this study was to evaluate 3.0T UTE for assessing LIO in thalassemia patients and directly compared with the standard 1.5T GRE as reference, particularly at severe overload with lower R2* values.

Materials and methods: Patients with thalassemia referred for liver iron assessment by MRI were prospectively enrolled. Each participant underwent liver iron quantification using both 1.5T GRE and 3.0T UTE sequences. For the latter, 4 different acquisition protocols were assessed: 7-echo free breathing (3.0T UTE 7E FB), 7-echo breath-hold (3.0T UTE 7E BH), 15-echo free breathing (3.0T UTE 15E FB), and 15-echo breath-hold (3.0T UTE 15E BH). The correlation between 1.5T GRE and each UTE sequence was analyzed. The agreement was further assessed using Bland-Altman analysis.

Results: Sixty-three patients were enrolled; 5 were excluded due to unmeasurably high liver iron concentration (LIC) by 1.5T MRI. The remaining 58 patients had a mean age of 34.3 ± 16.1 years; 24 (41.4%) were male, and 42 (72.4%) had thalassemia major. Regular transfusions were noted in 31 (53.4%). All 3.0T UTE sequences demonstrated excellent correlation with 1.5T GRE (R2, 0.9701-0.9827). Bland-Altman analysis indicated minimal bias and narrow limits of agreement. The 3.0T UTE 15E BH protocol yielded the strongest performance.

Conclusions: 3.0T UTE MRI sequences provide clinically feasible and accurate assessment of liver iron overload in thalassemia patients across a broad range of LIC values from 1.3 to 39.5 mg/g. These findings support the clinical utility of 3.0T UTE MRI for LIO detection and therapeutic decision-making in this population.

Objectives: Metal artifact reduction MRI can exceed specific absorption rate (SAR) limits due to high-bandwidth radiofrequency pulses, causing scan interruptions and prolonged acquisition times. The aim of the current study is to reduce SAR and potentially scan time in metal artifact reduction MRI using an optimized variable refocusing flip angle (VRFA) scheme compared with the standard constant refocusing flip angle (CRFA).

Materials and methods: Three VRFA variants (VRFA1 to VRFA3) were developed to maximize tissue signal and contrast while minimizing SAR and image blur. The optimal variant was selected through quantification of metal artifacts and image blur in phantoms and tissue signal in a volunteer. Patients with hip arthroplasty underwent CRFA and optimal VRFA imaging using high-bandwidth turbo-spin-echo (HBW-TSE) and compressed-sensing slice-encoding-for-metal-artifact-correction (CS-SEMAC) sequences. Three readers ranked paired CRFA and VRFA scans for quality. Analyses included repeated measures ANOVA, noninferiority testing, and paired t/Wilcoxon signed-rank tests.

Results: CRFA and VRFA1 to VRFA3 showed no significant differences in image blur (full-width-at-half-maximum, mean ± SD, 1.9 ± 0.2 vs 1.9 ± 0.2 vs 1.9 ± 0.3 vs 1.9 ± 0.3 pixels, P = 0.06) or metal artifacts (8.2 ± 2.8 vs 8.4 ± 2.7 vs 8.4 ± 2.6 vs 8.4 ± 2.7 pixels, P = 0.57). The optimal VRFA variant (VRFA3) preserved 81% of CRFA fat-muscle contrast at 77% SAR and 70% scan time on proton-density (PD), and 94% of fluid-muscle contrast at 80% SAR and 67% scan time on short-tau-inversion-recovery (STIR). In 23 patients [mean age, 67.3 y ± 12.2 (SD); 14 females], the optimal VRFA was noninferior to CRFA in all quality metrics (all 95% CI < noninferiority margin = 0.1) and significantly reduced SAR (mean, PD-HBW-TSE/STIR-HBW-TSE/PD-CS-SEMAC/STIR-CS-SEMAC: 1.11/1.35/1.17/1.18 vs 1.85/1.83/1.49/1.46 W/kg, all P ≤ 0.001). In HBW-TSE, reduced SAR allowed longer echo trains and 15% to 32% shorter scan times.

Conclusion: Metal artifact reduction MRI with VRFA reduces SAR without compromising image quality. It allows shorter acquisitions in HBW-TSE.

Objectives: Gadolinium-based contrast agents (GBCAs) are widely used in magnetic resonance imaging. Concerns exist regarding gadolinium deposition and its potential histopathologic tissue alterations, especially after repeated administrations of linear, less stable GBCAs. This study aimed to quantify gadolinium mass fractions in liver specimens of subjects exposed to GBCAs in correlation with histopathologic features.

Materials and methods: In this Institutional Review Board-approved study, mass fractions of gadolinium in human liver specimens ω(Gd) from 25 subjects who underwent liver tumor resection surgery and had received GBCA (1 to 9 times over 4 y), were quantitatively analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). Histomorphology was assessed based on the nonalcoholic fatty liver disease activity score (NAS). Linear regression analyses were performed with ω(Gd), time and dosage metrics, and histopathologic parameters.

Results: The median interval between last GBCA administration and surgery (T) was 14 days (range: 1 to 69 d). Gadolinium was detected in all liver samples (ω(Gd), median: 0.348 µg/g; range: 0.120 to 0.874 µg/g). No significant correlation was found between ω(Gd) and histologic scores, including inflammation and fibrosis. A strong negative correlation was found between ω(Gd) and ln(T) (P < 0.001). A positive correlation existed between ω(Gd) and the number (P = 0.010) but not the cumulative dose of previous GBCA administrations (P = 0.205).

Conclusions: Our results suggest that after intravenous administration of GBCA, a small fraction of gadolinium is retained in the liver over a time period of at least several weeks. A relationship was observed between Gadolinium retention and the number of GBCA administrations, but not with the cumulative dose and the degree of fatty liver disease.