NI-3 Magnetic resonance relaxometry for tumor cell density imaging for glioma: An exploratory study via 11C-methionine PET and its validation via stereotactic tissue sampling

Objective: While visualization of non-enhancing tumors for glioma is crucial for planning the most appropriate surgical or non-surgical treatment of the disease, current MRI cannot achieve this goal. This study aims to test the hypothesis that quantitative and diffusion MRI can estimate tumor burden with the brain. Materials and Methods: Study 1: Ten patients who have undergone Methionine PET (Met-PET), quantitative MRI (qMRI), and diffusion MRI (DWI) were included for analysis. A cut-off of a tumor-to-normal ratio (T/Nr) 1.5 was set on Met-PET, and the values from qMRI and DWI were compared. Study 2: Seventy-nine stereo-tactically sampled tissues from 22 glioma patients were correlated with Met-PET, qMRI, and DWI measurements regarding tumor cell density. qMRI acquisition: Imaging was performed on either a 1.5 or 3 T MR scanner (Prisma or Aera; Siemens Healthcare, Erlangen, Germany). T1-relaxometry was achieved by first acquiring MP2RAGE images, then converting those images into T1-relaxation time maps. At the same time, T2-relaxometry was achieved by first acquiring multi-echo T2-weighted images and then converting those images into T2-relaxation time maps, with both relaxometries performed via Bayesian inference modeling (Olea Nova+; Canon Medical Systems, Tochigi, Japan). Results: Study 1 revealed that regions of 1850ms < T1-relaxation time < 3200ms and 115ms < T2-relaxation time < 225ms tended to be Met-PET T/Nr > 1.5. DWI was not useful to separate areas between low and high Met-PET. Study 2 showed that regions of 1850ms < T1-relaxation time < 3200ms showed high tumor cell density than other areas (p=0.04). Conclusions: Our results supported the hypothesis that qMRI is useful for predicting the tumor load within the brain among glioma patients. T1-relaxation time was notably useful for this means. On the other hand, ADC measured from DWI was limited for tumor load prediction.

Quantification of contrast agent uptake in the hepatobiliary phase helps to differentiate hepatocellular carcinoma grade

This study aimed to assess the degree of differentiation of hepatocellular carcinoma (HCC) using Gd-EOB-DTPA-assisted magnetic resonance imaging (MRI) with T1 relaxometry. Thirty-three solitary HCC lesions were included in this retrospective study. This study's inclusion criteria were preoperative Gd-EOB-DTPA-assisted MRI of the liver and a histopathological evaluation after hepatic tumor resection. T1 maps of the liver were evaluated to determine the T1 relaxation time and reduction rate between the native phase and hepatobiliary phase (HBP) in liver lesions. These findings were correlated with the histopathologically determined degree of HCC differentiation (G1, well-differentiated; G2, moderately differentiated; G3, poorly differentiated). There was no significant difference between well-differentiated (950.2 ± 140.2 ms) and moderately/poorly differentiated (1009.4 ± 202.0 ms) HCCs in the native T1 maps. After contrast medium administration, a significant difference (p ≤ 0.001) in the mean T1 relaxation time in the HBP was found between well-differentiated (555.4 ± 140.2 ms) and moderately/poorly differentiated (750.9 ± 146.4 ms) HCCs. For well-differentiated HCCs, the reduction rate in the T1 time was significantly higher at 0.40 ± 0.15 than for moderately/poorly differentiated HCCs (0.25 ± 0.07; p = 0.006). In conclusion this study suggests that the uptake of Gd-EOB-DTPA in HCCs is correlated with tumor grade. Thus, Gd-EOB-DTPA-assisted T1 relaxometry can help to further differentiation of HCC.

Magnetic Resonance Relaxometry for Tumor Cell Density Imaging for Glioma: An Exploratory Study via 11C-methionine PET and Its Validation via Stereotactic Tissue Sampling

One of the most crucial yet challenging issues for glioma patient care is visualizing non-contrast-enhancing tumor regions. In this study, to test the hypothesis that quantitative magnetic resonance relaxometry reflects glioma tumor load within tissue and that it can be an imaging surrogate for visualizing non-contrast-enhancing tumors, we investigated the correlation between T1- and T2-weighted relaxation times, apparent diffusion coefficient (ADC) on magnetic resonance imaging, and 11C-methionine (MET) on positron emission tomography (PET). Moreover, we compared the T1- and T2-relaxation times and ADC with tumor cell density (TCD) findings obtained via stereotactic image-guided tissue sampling. Regions that presented a T1-relaxation time of >1850 ms but <3200 ms or a T2-relaxation time of >115 ms but <225 ms under 3 T indicated a high MET uptake. In addition, the stereotactic tissue sampling findings confirmed that the T1-relaxation time of 1850–3200 ms significantly indicated a higher TCD (p = 0.04). However, ADC was unable to show a significant correlation with MET uptake or with TCD. Finally, synthetically synthesized tumor load images from the T1- and T2-relaxation maps were able to visualize MET uptake presented on PET.

Paramagnetic contrast enhancement in MRI imaging of liver using an original hepatotropic high-affinity agent GDOF-Mn-DTPA

Background. The use of modern hepatotropic contrast compounds is associated with the risk of side-effects, like accumulation of metal ions in tissues and the development of systemic pathological reactions. Therefore, currently, obtaining of high-affinity hepatotropic drugs is under investigation.Objective. There was studied the dependence of specific contrast properties of the paramagnetic complex 2-(2-carboxymethyl-(4-hexa-decyloxyphenyl-carbamoyl-methyl))-aminoethyl-(4-hexadecyl-oxyphenylcarbamoyl methyl)-aminoacetic acid with manganese — GDOF-Mn-DTPA — in magnetic resonance imaging from the administered dose of the drug. Design and methods. The dynamics of changes in the liver contrast ratio over time at different dosages of the contrast compound GDOF-Mn-DTPA was evaluated, and changes in the T1 relaxation time of liver and kidney tissue of laboratory animals (Wistar rats, more than 300 g) at different dosages of GDOF-Mn-DTPA were calculated.Results. Visual analysis of contrast-enhanced MRI scans with GDOF-Mn-DTPA already at a dose of 0.025 mmol/kg reliably visualized the accumulation of paramagnet in the liver, while further concentration of the drug in the bile ducts of animals was noted, with the actual absence of visually detectable kidney contrast. When evaluating the T1 relaxation time for the liver and kidneys, a persistent decrease in the T1 time for liver tissue was obtained for doses of 0.1, 0.05 and 0.025 mmol/kg, in particular for 0.025 mmol/kg from the initial 760 (747–755) MS to 488 (474–505) MS (p < 0.02). On the contrary, the obtained values of T1 relaxation time for kidney tissue showed no significant accumulation of the paramagnetic contrast compound GDOF-Mn-DTPA to the renal parenchyma at a dosage of 0.025 mmol / kg or lower. GDOF-Mn-DTPA showed a high degree of hepatoselectivity, with a pronounced reduced excretion through the kidneys.Conclusion. The GDOF-Mn-DTPA complex is a stable compound with a high degree of selective contrast of the hepatic parenchyma, with minimal or no renal excretion, a reliable basis for a hepatoselective contrast agent for imaging and functional studies of the liver with MRI and clinical use in the near future.

Molecular Imaging of Inflammation and Fibrosis in Pressure Overload Heart Failure

Rationale: Tissue inflammation and subsequent fibrosis contribute to ventricle remodelling after ischemic injury, and have emerged as viable therapeutic targets. Comparatively little is understood about the dynamics of inflammation and fibrosis in non-ischemic heart failure, which is challenging to interrogate longitudinally. Objective: To investigate the interplay between ventricle loading conditions, tissue inflammation, and progressive fibrosis using non-invasive multimodality molecular imaging to characterize these processes in pressure overload heart failure. Methods and Results: We evaluated cardiac inflammation using positron emission tomography radiotracer 68Ga-pentixafor which binds to chemokine CXC-motif receptor 4 (CXCR4). Over the first 7d after transverse aortic constriction (TAC), CXCR4 imaging identified diffuse elevated myocardial inflammation throughout the left ventricle (+34%, p<0.001), returning to sham levels over 6 weeks after surgery. This transient signal colocalized to local enrichment of CD68 macrophages, as confirmed by autoradiography and immunostaining. Magnetic resonance imaging demonstrated a parallel prolongation of myocardial T1 relaxation time in TAC mice, persisting from 8d to 6 weeks after surgery (+22%, p=0.003). The persistent imaging signal correlated to increased tissue fibrosis on histology. Molecular imaging at 1 week after surgery correlated independently with the change in ventricle geometry over the subsequent 3 weeks (CXCR4, rpartial=0.670, p=0.024; T1, rpartial=0.689, p=0.019). Alleviation of ventricle pressure by mechanical unloading restored not only cardiac function and geometry, but also attenuated global inflammation and normalized T1 relaxation time. This finding demonstrates the capacity to monitor therapeutic intervention by serial molecular imaging. Conclusions: Inflammation and fibrosis are implicated in the early response to pressure overload, and may be sensitively monitored by multimodality imaging. Such multimodality molecular imaging approaches may guide novel therapeutic approaches in non-ischemic heart failure.

Longer sustained Fontan circulation is associated with prolonged hepatic T1 relaxation time on T1 mapping

Funding Acknowledgements Type of funding sources: None. Background Patients with single ventricle defects may develop Fontan-associated liver disease. T1 mapping has been successfully used for evaluating chronic liver disease in adults. Liver T1 mapping has been also studied in the pediatric patients with single ventricles, and these patients show higher T1 relaxation times compared to the healthy controls. Purpose Our objective was to study the relationship between the cardiac MRI (CMR) T1 mapping relaxation time of the liver and 1) CMR derived hemodynamic parameters, 2) peripheral venous pressure (PVP) measured from a cubital cannula 3) systemic ventricle morphology [LV vs. RV], 4) the age of patient, and 5) alanine transaminase (P-ALAT) levels. Methods This retrospective study included 46 patients with functional single ventricle, which underwent routine CMR at our hospital. Table 1 shows demographic and clinical data of the study population. Statistical analysis were performed with IBM SPSS Statistics v.25 software using independent samples t test, Mann-Whitney U-test or Pearson correlation as appropriate. A p-value less than 0.05 was considered significant. Results The average T1 relaxation time of the liver was longer in patients with RV morphology (p = 0.004). There was a significant moderate positive correlation between the age of the patients and hepatic T1 relaxation time (r = 0.45, p = 0.002), and between hepatic T1 relaxation time and P-ALAT levels (r = 0.5, p = 0.016) (Fig.1). No significant correlations were detected between the T1 times of the liver and hemodynamic parameters of the heart (all tested parameters are listed in the Table1). Ejection fraction and PVP showed a non-significant weak correlation with a hepatic T1 relaxation times (r=-0.3, p = 0,056 and r = 0.3, p = 0,070, respectively). Conclusions T1 mapping times of the liver may reflect Fontan-associated liver disease. We observed connections between the hepatic T1 relaxation times and 1) patients age, 2) systemic ventricle morphology and 3) P-ALAT levels.

Blood-brain barrier breakdown in non-enhancing multiple sclerosis lesions detected by 7-Tesla MP2RAGE ΔT1 mapping

Although the blood-brain barrier (BBB) is altered in most multiple sclerosis (MS) lesions, gadolinium enhancement is seen only in acute lesions. In this study, we aimed to investigate gadolinium-induced changes in T1 relaxation time in MS lesions on 7-tesla (7T) MRI as a means to quantify BBB breakdown in non-enhancing MS lesions. Forty-seven participants with MS underwent 7T MRI of the brain with a magnitude-prepared rapid acquisition of 2 gradient echoes (MP2RAGE) sequence before and after contrast. Subtraction of pre- and post-contrast T1 maps was used to measure T1 relaxation time change (ΔT1) from gadolinium. ΔT1 values were interrogated in enhancing white matter lesions (ELs), non-enhancing white matter lesions (NELs), and normal appearing white matter (NAWM) and metrics were compared to clinical data. ΔT1 was measurable in NELs (median: -0.139 (-0.304, 0.174) seconds; p < 0.001) and was negligible in NAWM (median: -0.001 (-0.036, 0.155) seconds; p = 0.516). Median ΔT1 in NELs correlated with disability as measured by Expanded Disability Status Scale (EDSS) (rho = -0.331, p = 0.026). Multiple measures of NEL ΔT1 variability also correlated with EDSS. NEL ΔT1 values were greater and more variable in patients with progressive forms of MS and greater in those not on MS treatment. Measurement of the changes in T1 relaxation time caused by contrast on 7T MP2RAGE reveals clinically relevant evidence of BBB breakdown in NELs in MS. This data suggests that NEL ΔT1 should be evaluated further as a biomarker for disease severity and treatment effect in MS.

A Multi-Modal MRI Analysis of Cortical Structure in Relation to Gender Dysphoria, Sexual Orientation, and Age in Adolescents

Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Sex-differentiated brain regions are hypothesized to reflect the experienced gender in GD and may play a role in sexual orientation development. Magnetic resonance brain images were acquired from 16 GD adolescents assigned female at birth (AFAB) not receiving hormone therapy, 17 cisgender girls, and 14 cisgender boys (ages 12–17 years) to examine three morphological and microstructural gray matter features in 76 brain regions: surface area (SA), cortical thickness (CT), and T1 relaxation time. Sexual orientation was represented by degree of androphilia-gynephilia and sexual attraction strength. Multivariate analyses found that cisgender boys had larger SA than cisgender girls and GD AFAB. Shorter T1, reflecting denser, macromolecule-rich tissue, correlated with older age and stronger gynephilia in cisgender boys and GD AFAB, and with stronger attractions in cisgender boys. Thus, cortical morphometry (mainly SA) was related to sex assigned at birth, but not experienced gender. Effects of experienced gender were found as similarities in correlation patterns in GD AFAB and cisgender boys in age and sexual orientation (mainly T1), indicating the need to consider developmental trajectories and sexual orientation in brain studies of GD.

Myocardial changes detected with modern cardiac magnetic resonance techniques in patients with early rheumatoid arthritis

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): HUS diagnostic imaging center Aims Subclinical myocardial disease is common in patients with rheumatoid arthritis (RA). Impaired cardiac function, myocardial fibrosis and inflammation have previously correlated with RA disease activity. Our aim was to study whether myocardial changes are detectable by cardiac magnetic resonance (CMR) at the time of RA diagnosis. Material and methods: We recruited 21 untreated early RA patients without history of heart disease in Helsinki University Hospital and Lohja Hospital (Finland) between 10/2018 and 2/2020, and nine healthy volunteers. The patients underwent a clinical examination, laboratory tests, and CMR including mapping of extracellular volume fraction (ECV), and T1 and T2 relaxation times. The healthy controls underwent non-contrast CMR. Results The RA patients were older than the controls (median 58.1 years vs. 41.6 years, respectively, table 1.). T1 was slightly higher in RA patients compared with healthy controls in anteroseptal segments (1015 ms vs. 982 ms, P = 0.017) (table 2). No difference in T2 was detected and the ECV values were considered normal. Segmental T1, T2 or ECV showed no significant correlations with age, duration of the symptoms or with RA disease activity (DAS28-CRP score). Conclusions The minor, but statistically significant, elevation of T1 relaxation time in the anteroseptal segments suggests that myocardial changes may occur already in the early phase of RA, the anteroseptal segments being most vulnerable. The elevation of T1 relaxation time can be caused by mild myocardial inflammation or fibrosis. Although no significant correlation with DAS28-CRP was observed, subclinical systemic inflammation may have contributed to the myocardial abnormalities. Table 1. Pre-contrast T1 relaxation time (ms) T2 relaxation time (ms) ECV (%) Mean RA patients Controls P-value RA patients Controls P-value RA patients Global myocardial mean 996 (978-1011) 982 (964-1000) 0.304 48.0 (44.6-49.7) 46.3 (44.1-48.7) 0.295 26.6 (25.7-28.5) Anterior segments 954 (919-1000) 951 (921-998) 0.929 47.7 (46.4-49.8) 47.9 (43.5-50.1) 0.871 26.7 (25.3-28.8) Anteroseptal segments 1015 (987-1041) 982 (947-996) 0.017 48.3 (45.5-49.9) 45.7 (43.8-48.4) 0.150 28.3 (26.8-29.2) Inferoseptal segments 1012 (992-1023) 998 (967-1003) 0.077 48.0 (43.5-49.4) 44.9 (43.5-46.2) 0.533 26.7 (26.0-27.9) Inferior segments 1016 (987-1064) 1003 (992-1025) 0.625 47.5 (45.1-50.3) 46.1 (44.2-48.4) 0.304 27.3 (25.6-29.0) Inferolateral segments 997 (974-1043) 992 (980-1016) &gt;0.999 46.6 (42.6-49.1) 45.1 (42.4-49.1) 0.689 25.8 (25.3-28.2) Anterolateral segments 973 (945-973) 981 (954-1010) 0.563 47.0 (45.1-48.5) 46.6 (43.5-49.6) 0.625 26.4 (24.7-28.0) T1 and T2 relaxation time mapping and ECV results. Abstract Figure. ECV mapping