RESUMEN

The potential of intranasal administered imaging agents to altogether bypass the blood-brain barrier offers a promising non-invasive approach for delivery directly to the brain. This review provides a comprehensive analysis of the advancements and challenges of delivering neuroimaging agents to the brain by way of the intranasal route, focusing on the various imaging modalities and their applications in central nervous system diagnostics and therapeutics. The various imaging modalities provide distinct insights into the pharmacokinetics, biodistribution, and specific interactions of imaging agents within the brain, facilitated by the use of tailored tracers and contrast agents. Methods: A comprehensive literature search spanned PubMed, Scopus, Embase, and Web of Science, covering publications from 1989 to 2024 inclusive. Starting with advancements in tracer development, we going to explore the rationale for integration of imaging techniques, and the critical role novel formulations such as nanoparticles, nano- and micro-emulsions in enhancing imaging agent delivery and visualisation. Results: The review highlights the use of innovative formulations in improving intranasal administration of neuroimaging agents, showcasing their ability to navigate the complex anatomical and physiological barriers of the nose-to-brain pathway. Various imaging techniques, MRI, PET, SPECT, CT, FUS and OI, were evaluated for their effectiveness in tracking these agents. The findings indicate significant improvements in brain targeting efficiency, rapid uptake, and sustained brain presence using innovative formulations. Conclusion: Future directions involve the development of optimised tracers tailored for intranasal administration, the potential of multimodal imaging approaches, and the implications of these advancements for diagnosing and treating neurological disorders.

Asunto(s)

RESUMEN

Background Neoadjuvant chemoimmunotherapy (NACI) has significantly increased the rate of pathologic complete response (pCR) in patients with early-stage triple-negative breast cancer (TNBC), although predictors of response to this regimen have not been identified. Purpose To investigate pretreatment perfusion MRI-based radiomics as a predictive marker for pCR in patients with TNBC undergoing NACI. Materials and Methods This prospective study enrolled women with early-stage TNBC who underwent NACI at two different centers from August 2021 to July 2023. Pretreatment dynamic contrast-enhanced MRI scans obtained using scanners from multiple vendors were analyzed using the Tofts model to segment tumors and analyze pharmacokinetic parameters. Radiomics features were extracted from the rate constant for contrast agent plasma-to-interstitial transfer (or Ktrans), volume fraction of extravascular and extracellular space (Ve), and maximum contrast agent uptake rate (Slopemax) maps and analyzed using unsupervised correlation and least absolute shrinkage and selector operator, or LASSO, to develop a radiomics score. Score effectiveness was assessed using the area under the receiver operating characteristic curve (AUC), and multivariable logistic regression was used to develop a multimodal nomogram for enhanced prediction. The discrimination, calibration, and clinical utility of the nomogram were evaluated in an external test set. Results The training set included 112 female participants from center 1 (mean age, 52 years ± 11 [SD]), and the external test set included 83 female participants from center 2 (mean age, 47 years ± 11). The radiomics score demonstrated an AUC of 0.80 (95% CI: 0.70, 0.89) for predicting pCR. A nomogram incorporating the radiomics score, grade, and Ki-67 yielded an AUC of 0.86 (95% CI: 0.78, 0.94) in the test set. Associations were found between higher radiomics score (>0.25) and tumor size (P < .001), washout enhancement (P = .01), androgen receptor expression (P = .009), and programmed death ligand 1 expression (P = .01), demonstrating a correlation with tumor immune environment in participants with TNBC. Conclusion A radiomics score derived from pharmacokinetic parameters at pretreatment dynamic contrast-enhanced MRI exhibited good performance for predicting pCR in participants with TNBC undergoing NACI, and could potentially be used to enhance clinical decision making. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Rauch in this issue.

Asunto(s)

Asunto(s)

RESUMEN

BACKGROUND AND PURPOSE: Analysis of vessel wall contrast kinetics (ie, wash-in/washout) is a promising method for the diagnosis and risk-stratification of intracranial atherosclerotic disease plaque (ICAD-P) and the intracranial aneurysm walls (IA-W). We used black-blood MR imaging or MR vessel wall imaging to evaluate the temporal relationship of gadolinium contrast uptake kinetics in ICAD-Ps and IA-Ws compared with normal anatomic reference structures. MATERIALS AND METHODS: Patients with ICAD-Ps or IAs who underwent MR vessel wall imaging with precontrast, early postcontrast (5-15 minutes), and delayed postcontrast (20-30 minutes) 3D T1-weighted TSE sequences were retrospectively studied. ROIs of a standardized diameter (2 mm) were used to measure the signal intensities of the cavernous sinus, pituitary infundibulum, temporalis muscle, and choroid plexus. Point ROIs were used for ICAD-Ps and IA-Ws. All ROI signal intensities were normalized to white matter signal intensity obtained using ROIs of 10-mm diameter. Measurements were acquired on precontrast, early postcontrast, and delayed postcontrast 3D T1 TSE sequences for each patient.ajnr;45/9/1206/T1T1T1Table 1:MR-VWI parameters for ICAD-Ps and IAsParameterValueSequence3D TSEScan planeAxialFOV (mm)160TR/TE (ms)800/28-32BW (Hx/pixel)370θ120Acceleration2ETL42Matrix acquisition0.5 mm ×0.5 mmMatrix recon0.5 mm ×0.5 mmNo. of slices/thick120/0.5Note:-FOV indicates field of view; TR, the repetition time; TE, the echo time; BW, bandwidth; ETL, echo train length; Matrix recon, matrix reconstruction. RESULTS: Ten patients with 17 symptomatic ICAD-Ps and 30 patients with 34 IA-Ws were included and demonstrated persisting contrast uptake (P < .001) of 7.21% and 10.54% beyond the early phase (5-15 minutes postcontrast) and in the delayed phase (20-30 minutes postcontrast) on postcontrast MR vessel wall imaging. However, normal anatomic reference structures including the pituitary infundibulum and cavernous sinus demonstrated a paradoxical contrast washout in the delayed phase. In both ICAD-Ps and IA-Ws, the greatest percentage of quantitative enhancement (>70%-90%) occurred in the early phase of postcontrast imaging, consistent with the rapid contrast uptake kinetics of neurovascular pathology. CONCLUSIONS: Using standard MR vessel wall imaging techniques, our results demonstrate the effects of gadolinium contrast uptake kinetics in ICAD-Ps and IA-Ws with extended accumulating enhancement into the delayed phase (> 15 minutes) as opposed to normal anatomic reference structures that conversely exhibit decreasing enhancement. Because these relative differences are used to assess qualitative patterns of ICAD-P and IA-W enhancement, our findings highlight the importance of standardizing acquisition time points and MR vessel wall imaging protocols to interpret pathologic enhancement for the risk stratification of cerebrovascular pathologies.

Asunto(s)

RESUMEN

BACKGROUND AND PURPOSE: After repeat administration of gadolinium-based contrast agents (GBCAs), the association between gadolinium retention in the central and peripheral nervous systems and the main manifestations of myelopathy and progressive neurologic symptoms remains unclear. We investigated the effects of the repeat administration of GBCAs on gadolinium retention in the central and peripheral nervous systems and the sensory, cognitive, and athletic implications. MATERIALS AND METHODS: Forty-eight male Wistar rats (6 weeks of age) were randomly divided into 4 experimental groups (12 rats in each group): the gadodiamide group (linear and nonionic GBCAs), the gadopentetate dimeglumine group (linear and ionic GBCAs), the gadoterate meglumine group (macrocyclic and ionic GBCAs), and the control group (0.9% saline solution). The brains of the rats were scanned using 9.4T MRI. Sensory behavioral tests were performed to assess the effect of GBCAs on pain sensitivity function. Gadolinium deposition in the brain, spinal cord, and peripheral nerves was determined by inductively coupled plasma mass-spectrometry. Transmission electron microscopy was used to observe the microscopic distribution of gadolinium after deposition in the spinal cord. The histopathologic features in the spinal cord were analyzed by H&E staining, Nissl staining, glial fibrillary acidic protein staining, and neuron-specific enolase staining after administration of GBCAs. RESULTS: All GBCAs resulted in gadolinium deposition in the central and peripheral nerve tissues, with the highest deposition in the sciatic nerve tissue (mean, 62.86 [SD, 12.56] nmol/g). Decreased muscle power, impairment of spatial cognitive function power, and pain hypersensitivity to thermal and mechanical stimuli were observed after exposure to gadodiamide. At the spinal cord, transmission electron microscopy found that the region of gadolinium depositions had a spheric structure similar to "sea urchins" and was mainly located near the vascular basement membrane. CONCLUSIONS: Multiple injections of GBCAs caused gadolinium deposition in the brain, spinal cord, and peripheral nerves, especially in the spinal cords of the gadodiamide group. Gadodiamide led to pain hypersensitivity and decreased muscle power and cognitive ability. For the patients who are hypersensitive to pain and need multiple MRI examinations, we recommend using macrocyclic GBCAs and the lowest dose possible.

Asunto(s)

RESUMEN

Purpose: To use hepatic uptake index (HUI) of liver lobes on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) to discriminate between patients with hepatitis B-related cirrhosis in compensated and decompensated statuses. Methods: Forty-four consecutive patients with hepatitis B-related cirrhosis who underwent Gd-EOB-DTPA-enhanced MRI were divided into compensated and decompensated statuses based on clinical evaluation. Volume and signal intensity of individual lobes were retrospectively measured to calculate HUI of the right liver lobe (RHUI), medial (MHUI) and lateral (LHUI) left liver lobes, and caudate lobe (CHUI). Spearman's rank correlation analyses were performed to evaluate relationships of lobe-based HUI with Child-Pugh and model for end-stage liver disease (MELD) scoring system scores in compensated and decompensated statuses. The Mann-Whitney U-test was used to compare the lobe-based HUI between compensated and decompensated statuses. The performance of lobe-based HUI in distinguishing cirrhosis was evaluated using receiver operating characteristic (ROC) analysis, and the area under the ROC curve (AUC) was calculated as a measure of accuracy. Delong's method was used for statistical analysis to elucidate which HUI is optimal. Results: Compensated and decompensated liver cirrhosis were confirmed in 25 (56.82%) and 19 (43.18%) patients, respectively. According to Spearman's rank correlation analysis, RHUI, MHUI, LHUI, and CHUI were all significantly associated with Child-Pugh and MELD scores (all P values <0.05). Receiver operating characteristic analysis demonstrated that among all lobe-based HUI parameters, RHUI could best perform the previous discrimination with a cut-off of 485.73 and obtain an AUC of 0.867. The AUC of RHUI improved and was significantly different from that of MHUI, LHUI, and CHUI (P = 0.03, P = 0.007, and P < 0.001, respectively, Delong's test). Conclusions: The RHUI could help quantitatively discriminate hepatitis B-related cirrhosis between compensated and decompensated statuses.

Asunto(s)

RESUMEN

BACKGROUND: Iron oxide nanoparticles (IONPs) have been cleared by the Food and Drug Administration (FDA) for various clinical applications, such as tumor-targeted imaging, hyperthermia therapy, drug delivery, and live-cell tracking. However, the application of IONPs as T1 contrast agents has been restricted due to their high r2 values and r2/r1 ratios, which limit their effectiveness in T1 contrast enhancement. Notably, IONPs with diameters smaller than 5 nm, referred to as extremely small-sized IONPs (ESIONs), have demonstrated potential in overcoming these limitations. To advance the clinical application of ESIONs as T1 contrast agents, we have refined a scale-up process for micelle encapsulation aimed at improving the hydrophilization of ESIONs, and have carried out comprehensive in vivo biodistribution and preclinical toxicity assessments. RESULTS: The optimization of the scale-up micelle-encapsulation process, specifically employing Tween60 at a concentration of 10% v/v, resulted in ESIONs that were uniformly hydrophilized, with an average size of 9.35 nm and a high purification yield. Stability tests showed that these ESIONs maintained consistent size over extended storage periods and dispersed effectively in blood and serum-mimicking environments. Relaxivity measurements indicated an r1 value of 3.43 mM- 1s- 1 and a favorable r2/r1 ratio of 5.36, suggesting their potential as T1 contrast agents. Biodistribution studies revealed that the ESIONs had extended circulation times in the bloodstream and were primarily cleared via the hepatobiliary route, with negligible renal excretion. We monitored blood clearance and organ distribution using positron emission tomography and magnetic resonance imaging (MRI). Additionally, MRI signal variations in a dose-dependent manner highlighted different behaviors at varying ESIONs concentrations, implying that optimal dosages might be specific to the intended imaging application. Preclinical safety evaluations indicated that ESIONs were tolerable in rats at doses up to 25 mg/kg. CONCLUSIONS: This study effectively optimized a scale-up process for the micelle encapsulation of ESIONs, leading to the production of hydrophilic ESIONs at gram-scale levels. These optimized ESIONs showcased properties conducive to T1 contrast imaging, such as elevated r1 relaxivity and a reduced r2/r1 ratio. Biodistribution study underscored their prolonged bloodstream presence and efficient clearance through the liver and bile, without significant renal involvement. The preclinical toxicity tests affirmed the safety of the ESIONs, supporting their potential use as T1 contrast agent with versatile clinical application.

Asunto(s)

RESUMEN

Implementing shortened one-compartment iohexol plasma clearance models for GFR measurement is crucial since the gold standard inulin renal clearance technique and the reference two-compartment, 10-hour, 16-samplings iohexol plasma clearance method are clinically unfeasible. Inulin may precipitate anaphylactic shock. Four-hour and 8-hour one-compartment iohexol plasma clearance models with Bröchner-Mortensen correction provide accurate GFR measurements in patients with estimated GFR (eGFR) > or ≤40 mL/min/1.73m2, respectively. We compared the performance of the simplified 5-hour, 4-samplings, two-compartment population pharmacokinetic model (popPK) with the performance of the reference two-compartment 10-hour iohexol method in 16 patients with GFR 15.2 to 56.5 mL/min/1.73 m2. We also compared the performance of shortened (5, 6 and 7-hour) one-compartment models with the performance of the standard 8-hour one-compartment model in 101 patients with eGFR ≤40 mL/min/1.73 m2. The performance of popPK and shortened methods versus reference methods was evaluated by total deviation index (TDI), concordance correlation coefficient (CCC) and coverage probability (CP). TDI <10%, CCC ≥0.9 and CP >90% indicated adequate performance. TDI, CCC and CP of popPK were 11.11%, 0.809 and 54.10%, respectively. All shortened, one-compartment models overestimated the GFR (p <0.0001 for all) as compared to the 8-hour model. TDI, CCC and CP were 7.02%, 0.815, and 75.80% for the 7-hour model, 7.26%, 0.803, and 74.20% for the 6-hour model, and 8.85%, 0.729 and 64.70% for the 5-hour model. The agreement of popPK model was comparable to that obtained with the Chronic-Kidney-Disease-Collaboration-Epidemiology (CKD-Epi) and the Modification-of-Diet-in-Renal-Disease (MDRD) serum-creatinine based equations for GFR estimation. PopPK model is remarkably unreliable for GFR measurement in stage III-IV CKD patients. In patients with eGFR ≤40 mL/min/1.73m2, shortened one-compartment models, in particular the 5-hour model, are less performant than the reference 8-hour model. For accurate GFR measurements, the iohexol plasma clearance should be measured with appropriate protocols. Over-simplified procedures should be avoided.

Asunto(s)

RESUMEN

BACKGROUND: Despite the efficacy of absolute ethanol (EtOH), its radiolucency introduces several risks in interventional therapy for treating vascular malformations. This study aims to develop a novel radiopaque ethanol injection (REI) to address this issue. METHODS: Iopromide is mixed with ethanol to achieve radiopacity and improve the physicochemical properties of the solution. Overall, 82 male New Zealand white rabbits are selected for in vivo radiopacity testing, peripheral vein sclerosis [animals were divided into the following 5 groups (n = 6): negative control (NC, saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), low-dose REI (L-D REI, 0.125 ml/kg), moderate-dose REI (M-D REI, 0.250 ml/kg), and high-dose REI (H-D REI 0.375 ml/kg)], pharmacokinetic analyses (the blood sample was harvested before injection, 5 min, 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, and 8 h after injection in peripheral vein sclerosis experiment), peripheral artery embolization [animals were divided into the following 5 groups (n = 3): NC (saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)], kidney transcatheter arterial embolization [animals were divided into the following 4 groups (n = 3): positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg); each healthy kidney was injected with saline as negative control], and biosafety evaluations [animals were divided into the following 5 groups (n = 3): NC (0.250 ml/kg), high-dose EtOH (0.375 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)]. Then, a prospective cohort study involving 6 patients with peripheral venous malformations (VMs) is performed to explore the clinical safety and effectiveness of REI. From Jun 1, 2023 to August 31, 2023, 6 patients [age: (33.3 ± 17.2) years] with lingual VMs received sclerotherapy of REI and 2-month follow-up. Adverse events and serious adverse events were evaluated, whereas the efficacy of REI was determined by both the traceability of the REI under DSA throughout the entire injection and the therapeutic effect 2 months after a single injection. RESULTS: The REI contains 81.4% ethanol (v/v) and 111.3 mg/ml iodine, which can be traced throughout the injection in the animals and patients. The REI also exerts a similar effect as EtOH on peripheral venous sclerosis, peripheral arterial embolization, and renal embolization. Furthermore, the REI can be metabolized at a similar rate compared to EtOH and Ultravist® and did not cause injury to the animals' heart, liver, spleen, lungs, kidneys and brain. No REI-related adverse effects have occurred during sclerotherapy of VMs, and 4/6 patients (66.7%) have achieved complete response at follow-up. CONCLUSION: In conclusion, REI is safe, exerts therapeutic effects, and compensates for the radiolucency of EtOH in treating VMs. TRIAL REGISTRATION: The clinical trial was registered as No. ChiCTR2300071751 on May 24 2023.

Asunto(s)

RESUMEN

A novel brain-targeted and reactive oxygen species-activatable manganese dioxide containing nanoparticle system functionalized with anti-amyloid-ß antibody (named aAß-BTRA-NC) developed by our group has shown great promise as a highly selective magnetic resonance imaging (MRI) contrast agent for early detection and multitargeted disease-modifying treatment of Alzheimer's disease (AD). To further evaluate the suitability of the formulation for future clinical application, we investigated the safety, biodistribution, and pharmacokinetic profile of aAß-BTRA-NC in a transgenic TgCRND8 mouse AD model, wild type (WT) littermate, and CD-1 mice. Dose-ascending studies demonstrated that aAß-BTRA-NC was well-tolerated by the animals up to 300 µmol Mn/kg body weight [b.w.], 3 times the efficacious dose for early AD detection without apparent adverse effects; Histopathological, hematological, and biochemical analyses indicated that a single dose of aAß-BTRA-NC did not cause any toxicity in major organs. Immunotoxicity data showed that aAß-BTRA-NC was safer than commercially available gadolinium-based MRI contrast agents at an equivalent dose of 100 µmol/kg b.w. of metal ions. Intravenously administered aAß-BTRA-NC was taken up by main organs with the order of liver, kidneys, intestines, spleen, followed by other organs, and cleared after one day to one week post injection. Pharmacokinetic analysis indicated that the plasma concentration profile of aAß-BTRA-NC followed a 2-compartmental model with faster clearance in the AD mice than in the WT mice. The results suggest that aAß-BTRA-NC exhibits a strong safety profile as a nanotheranostic agent which warrants more robust preclinical development for future clinical applications.

Asunto(s)

RESUMEN

BACKGROUND: There are several shortcomings in present methods for estimation of GFR from plasma clearance. The aim of the present study was therefore to develop a physiologically based method for calculation of plasma clearance of iohexol. METHODS: A mechanistic model founded on classical biochemical engineering principles where in- and outgoing molecular flows of iohexol between plasma and surrounding tissues were balanced over time. After intravenous injections of iohexol, plasma samples were taken from the investigated subjects until complete elimination of iohexol. After tuning of the model parameters, the clearance value was calculated from the injected dose and the integral of the iohexol concentrations over the investigated period. RESULTS: The mass balance model was able to predict the time course of iohexol distribution and elimination after parameterization of mass balance and kinetic equations. Four model structures were evaluated, all based on model parameters derived from published data and from internal tests, each complied at varying physiological conditions. Iohexol clearance was assessed through the model and compared with calculations from previously practiced methods. When testing the mass balance model on ten healthy subjects, clearance was estimated accurately. CONCLUSIONS: The physiological and mechanistic character of the mass balance model may suggest that its derived clearance comes closer to actual in vivo conditions than data derived from previously practiced calculation methods. Although here, only verified with the clearance marker iohexol, the mass balance model should be applicable also to other renal clearance markers.

Asunto(s)

RESUMEN

Background: Medical imaging modalities, such as magnetic resonance imaging (MRI), ultrasound, and fluorescence imaging, have gained widespread acceptance in clinical practice for tumor diagnosis. Each imaging modality has its own unique principles, advantages, and limitations, thus necessitating a multimodal approach for a comprehensive disease understanding of the disease process. To enhance diagnostic precision, physicians frequently integrate data from multiple imaging modalities, driving research advancements in multimodal imaging technology research. Methods: In this study, hematoporphyrin-poly (lactic acid) (HP-PLLA) polymer was prepared via ring-opening polymerization and thoroughly characterized using FT-IR, 1H-NMR, XRD, and TGA. HP-PLLA based nanoparticles encapsulating perfluoropentane (PFP) and salicylic acid were prepared via emulsion-solvent evaporation. Zeta potential and mean diameter were assessed using DLS and TEM. Biocompatibility was evaluated via cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed with a dedicated apparatus, while CEST MRI was conducted using a 7.0 T animal scanner. Results: We designed and prepared a novel dual-mode nanoimaging probe SA/PFP@HP-PLLA NPs. PFP enhanced US imaging, while salicylic acid bolstered CEST imaging. With an average size of 74.43 ± 1.12 nm, a polydispersity index of 0.175 ± 0.015, and a surface zeta potential of -64.1 ± 2.11 mV. These NPs exhibit excellent biocompatibility and stability. Both in vitro and in vivo experiments confirmed the SA/PFP@HP-PLLA NP's ability to improve tumor characterization and diagnostic precision. Conclusion: The SA/PFP@HP-PLLA NPs demonstrate promising dual-modality imaging capabilities, indicating their potential for preclinical and clinical use as a contrast agent.

Asunto(s)

RESUMEN

Contrast transport models are widely used to quantify blood flow and transport in dynamic contrast-enhanced magnetic resonance imaging. These models analyze the time course of the contrast agent concentration, providing diagnostic and prognostic value for many biological systems. Thus, ensuring accuracy and repeatability of the model parameter estimation is a fundamental concern. In this work, we analyze the structural and practical identifiability of a class of nested compartment models pervasively used in analysis of MRI data. We combine artificial and real data to study the role of noise in model parameter estimation. We observe that although all the models are structurally identifiable, practical identifiability strongly depends on the data characteristics. We analyze the impact of increasing data noise on parameter identifiability and show how the latter can be recovered with increased data quality. To complete the analysis, we show that the results do not depend on specific tissue characteristics or the type of enhancement patterns of contrast agent signal.

Asunto(s)

RESUMEN

BACKGROUND: The pathway by which drugs are injected subcutaneously behind the ear to act on the inner ear has not been fully elucidated. OBJECTIVES: To compare the uptake of gadopentetate dimeglumine (Gd-DTPA) and dexamethasone (Dex) in the cochlea and facial nerve of rats following different administrations. MATERIALS AND METHODS: Magnetic resonance imaging was applied to observe the distribution of Gd-DTPA in the facial nerve and inner ear. We observed the uptake of Dex after it was injected with different methods. RESULTS: Images of the intravenous (IV) and intramuscular (IM) groups showed that the bilateral cochlea of the rat was visualized almost simultaneously. While in the left post-auricular (PA) injection group, it was asynchronous. The maximum accumulation (Cmax) of the Gd in the left facial nerve of the PA group (35.406 ± 5.32) was substantially higher than that of the IV group (16.765 ± 3.7542) (p < .01). CONCLUSIONS: Compared with systemic administration, PA has the advantages of long Gd and Dex action time and high accumulation concentration to treat facial nerve diseases. SIGNIFICANCE: The distribution of Gd and Dex in the inner ear and facial nerve of rats following PA injection might be unique.

Asunto(s)

RESUMEN

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with an extended Tofts linear (ETL) model for tissue and tumor evaluation has been established, but its effectiveness in evaluating the pancreas remains uncertain. PURPOSE: To understand the pharmacokinetics of normal pancreas and serve as a reference for future studies of pancreatic diseases. MATERIAL AND METHODS: Pancreatic pharmacokinetic parameters of 54 volunteers were calculated using DCE-MRI with the ETL model. First, intra- and inter-observer reliability was assessed through the use of the intra-class correlation coefficient (ICC) and coefficient of variation (CoV). Second, a subgroup analysis of the pancreatic DCE-MRI pharmacokinetic parameters was carried out by dividing the 54 individuals into three groups based on the pancreatic region, three groups based on age, and two groups based on sex. RESULTS: There was excellent agreement and low variability of intra- and inter-observer to pancreatic DCE-MRI pharmacokinetic parameters. The intra- and inter-observer ICCs of Ktrans, kep, ve, and vp were 0.971, 0.952, 0.959, 0.944 and 0.947, 0.911, 0.978, 0.917, respectively. The intra- and inter-observer CoVs of Ktrans, kep, ve, vp were 9.98%, 5.99%, 6.47%, 4.76% and 10.15%, 5.22%, 6.28%, 5.40%, respectively. Only the pancreatic ve of the older group was higher than that of the young and middle-aged groups (P = 0.042, 0.001), and the vp of the pancreatic head was higher than that of the pancreatic body and tail (P = 0.014, 0.043). CONCLUSION: The application of DCE-MRI with an ETL model provides a reliable, robust, and reproducible means of non-invasively quantifying pancreatic pharmacokinetic parameters.

Asunto(s)

RESUMEN

PURPOSE: To develop a digital reference object (DRO) toolkit to generate realistic breast DCE-MRI data for quantitative assessment of image reconstruction and data analysis methods. METHODS: A simulation framework in a form of DRO toolkit has been developed using the ultrafast and conventional breast DCE-MRI data of 53 women with malignant (n = 25) or benign (n = 28) lesions. We segmented five anatomical regions and performed pharmacokinetic analysis to determine the ranges of pharmacokinetic parameters for each segmented region. A database of the segmentations and their pharmacokinetic parameters is included in the DRO toolkit that can generate a large number of realistic breast DCE-MRI data. We provide two potential examples for our DRO toolkit: assessing the accuracy of an image reconstruction method using undersampled simulated radial k-space data and assessing the impact of the B 1 + $$ {\mathrm{B}}_1^{+} $$ field inhomogeneity on estimated parameters. RESULTS: The estimated pharmacokinetic parameters for each region showed agreement with previously reported values. For the assessment of the reconstruction method, it was found that the temporal regularization resulted in significant underestimation of estimated parameters by up to 57% and 10% with the weighting factor λ = 0.1 and 0.01, respectively. We also demonstrated that spatial discrepancy of v p $$ {v}_p $$ and PS $$ \mathrm{PS} $$ increase to about 33% and 51% without correction for B 1 + $$ {\mathrm{B}}_1^{+} $$ field. CONCLUSION: We have developed a DRO toolkit that includes realistic morphology of tumor lesions along with the expected pharmacokinetic parameter ranges. This simulation framework can generate many images for quantitative assessment of DCE-MRI reconstruction and analysis methods.

Asunto(s)

RESUMEN

AGuIX, a novel gadolinium-based nanoparticle, has been deployed in a pioneering double-blinded Phase II clinical trial aiming to assess its efficacy in enhancing radiotherapy for tumor treatment. This paper moves towards this goal by analyzing AGuIX uptake patterns in 23 patients. A phantom was designed to establish the relationship between AGuIX concentration and longitudinal ( T 1 ) relaxation. A 3T MRI and MP2RAGE sequence were used to generate patient T 1 maps. AGuIX uptake in tumors was determined based on longitudinal relaxivity. AGuIX (or placebo) was administered to 23 patients intravenously at 100 mg/kg 1-5 hours pre-imaging. Each of 129 brain metastases across 23 patients were captured in T 1 maps and examined for AGuIX uptake and distribution. Inferred AGuIX recipients had average tumor uptakes between 0.012 and 0.17 mg/ml, with a mean of 0.055 mg/ml. Suspected placebo recipients appeared to have no appreciable uptake. Tumors presented with varying spatial AGuIX uptake distributions, suspected to be related to differences in accumulation time and patient-specific bioaccumulation factors. This research demonstrates AGuIX's ability to accumulate in brain metastases, with quantifiable uptake via T 1 mapping. Future analyses will extend these methods to complete clinical trial data (~ 134 patients) to evaluate the potential relationship between nanoparticle uptake and possible tumor response following radiotherapy.Clinical Trial Registration Number: NCT04899908.Clinical Trial Registration Date: 25/05/2021.

Asunto(s)

RESUMEN

PURPOSE: Gadolinium (Gd)-based contrast agents are primarily used for contrast-enhanced magnetic resonance lymphangiography (MRL). However, overcoming venous contamination issues remains challenging. This study aims to assess the MRL efficacy of the newly developed iron-based contrast agent (INV-001) that is specially designed to mitigate venous contamination issues. The study further explores the optimal dosage, including both injection volume and concentration, required to achieve successful visualization of the popliteal lymph nodes and surrounding lymphatic vessels. PROCEDURES: All animals utilized in this study were male Sprague-Dawley (SD) rats weighing between 250 and 300 g. The contrast agents prepared were injected intradermally in the fourth phalanx of both hind limbs using a 30-gauge syringe in SD rats. MRL was performed every 16 min on a coronal 3D time-of-flight sequence with saturation bands using a 9.4-T animal machine. RESULTS: Contrary to Gd-DOTA, which exhibited venous contamination in most animals irrespective of injection dosages and conditions, INV-001 showed no venous contamination. For Gd-DOTA, the popliteal lymph nodes and lymphatic vessels reached peak enhancement 16 min after injection from the injection site and then rapidly washed out. However, with INV-001, they reached peak enhancement between 16 and 32 min after injection, with prolonged visualization of the popliteal lymph node and lymphatic vessels. INV-001 at 0.45 µmol (15 mM, 30 µL) and 0.75 µmol (15 mM, 50 µL) achieved high scores for qualitative image analysis, providing good visualization of the popliteal lymph nodes and lymphatic vessels without issues of venous contamination, interstitial space enhancement, or lymph node enlargement. CONCLUSION: In MRL, INV-001, a novel T1 contrast agent based on iron, enables prolonged enhancement of popliteal lymph nodes and lymphatic vessels without venous contamination.

Asunto(s)

RESUMEN

Over the last decade, it has become evident that cerebrospinal fluid (CSF) plays a pivotal role in brain solute clearance through perivascular pathways and interactions between the brain and meningeal lymphatic vessels. Whereas most of this fundamental knowledge was gained from rodent models, human brain clearance imaging has provided important insights into the human system and highlighted the existence of important interspecies differences. Current gold standard techniques for human brain clearance imaging involve the injection of gadolinium-based contrast agents and monitoring their distribution and clearance over a period from a few hours up to 2 days. With both intrathecal and intravenous injections being used, which each have their own specific routes of distribution and thus clearance of contrast agent, a clear understanding of the kinetics associated with both approaches, and especially the differences between them, is needed to properly interpret the results. Because it is known that intrathecally injected contrast agent reaches the blood, albeit in small concentrations, and that similarly some of the intravenously injected agent can be detected in CSF, both pathways are connected and will, in theory, reach the same compartments. However, because of clear differences in relative enhancement patterns, both injection approaches will result in varying sensitivities for assessment of different subparts of the brain clearance system. In this opinion review article, the "EU Joint Programme - Neurodegenerative Disease Research (JPND)" consortium on human brain clearance imaging provides an overview of contrast agent pharmacokinetics in vivo following intrathecal and intravenous injections and what typical concentrations and concentration-time curves should be expected. This can be the basis for optimizing and interpreting contrast-enhanced MRI for brain clearance imaging. Furthermore, this can shed light on how molecules may exchange between blood, brain, and CSF.

Asunto(s)

RESUMEN

PURPOSE: The intervertebral disc being avascular depends on diffusion and load-based convection for essential nutrient supply and waste removal. There are no reliable methods to simultaneously investigate them in humans under natural loads. For the first time, present study aims to investigate this by strategically employing positional MRI and post-contrast studies in three physiological positions: supine, standing and post-standing recovery. METHODS: A total of 100 healthy intervertebral discs from 20 volunteers were subjected to a serial post-contrast MR study after injecting 0.3 mmol/kg gadodiamide and T1-weighted MR images were obtained at 0, 2, 6, 12 and 24 h. At each time interval, images were obtained in three positions, i.e. supine, standing and post-standing recovery supine. The signal intensity values at endplate zone and nucleus pulposus were measured. Enhancement percentages were calculated and analysed comparing three positions. RESULTS: During unloaded supine position, there was slow gradual increase in enhancement reaching peak at 6 h. When the subjects assumed standing position, there was immediate loss of enhancement at nucleus pulposus which resulted in reciprocal increase in enhancement at endplate zone (washout phenomenon). Interestingly, when subjects assumed the post-standing recovery position, the nucleus pulposus regained the enhancement and endplate zone showed reciprocal loss (pumping-in phenomenon). CONCLUSIONS: For the first time, present study documented acute effects of physiological loading and unloading on nutrition of human discs in vivo. While during rest, solutes diffused gradually into disc, the diurnal short loading and unloading redistribute small solutes by convection. Standing caused rapid solute depletion but promptly regained by assuming resting supine position.

Asunto(s)