Purpose

To develop a new technique that enables simultaneous quantification of whole-brain T₁ , T₂ , T2∗ , as well as susceptibility and synthesis of six contrast-weighted images in a single 9.1-minute scan.

Methods

The technique uses hybrid T₂ -prepared inversion-recovery pulse modules and multi-echo gradient-echo readouts to collect k-space data with various T1, T2, and T2∗ weightings. The underlying image is represented as a six-dimensional low-rank tensor consisting of three spatial dimensions and three temporal dimensions corresponding to T₁ recovery, T₂ decay, and multi-echo behaviors, respectively. Multiparametric maps were fitted from reconstructed image series. The proposed method was validated on phantoms and healthy volunteers, by comparing quantitative measurements against corresponding reference methods. The feasibility of generating six contrast-weighted images was also examined.

Results

High quality, co-registered T₁ , T₂ , and T2∗ susceptibility maps were generated that closely resembled the reference maps. Phantom measurements showed substantial consistency (R² > 0.98) with the reference measurements. Despite the significant differences of T₁ (p < .001), T₂ (p = .002), and T2∗ (p = 0.008) between our method and the references for in vivo studies, excellent agreement was achieved with all intraclass correlation coefficients greater than 0.75. No significant difference was found for susceptibility (p = .900). The framework is also capable of synthesizing six contrast-weighted images.

Conclusion

The MR Multitasking-based 3D brain mapping of T₁ , T₂ , T2∗ , and susceptibility agrees well with the reference and is a promising technique for multicontrast and quantitative imaging.

Estimates of the spectrum and frequency of pathogenic variants in Parkinsons disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinsons disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD.