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Ness, K. K.

Publications and source records attributed to Ness, K. K..

2 recordsLinked to original sources

Enhanced Temporal-Resolution CEST Imaging method for reliable mapping of muscle OXPHOS

PurposeTo develop and validate a novel chemical exchange saturation transfer (CEST) MRI method to map skeletal muscle OXPHOS (Oxidative Phosphorylation CEST or OXCEST). Theory and MethodsOur proposed OXCEST method acquires creatine (Cr)-weighted CEST maps by applying RF saturation (B1) at only two frequency offsets: +1.8 ppm (targeting the Cr amine resonance) and -1.8 ppm (to calculate MTRasym at 1.8 ppm). The pre-exercise MTRasym is modeled as a second-order polynomial function (f) of B0. Next, the post-exercise alteration in MTRasym is hypothesized to be affected by both an exercise-induced increase in Cr and changes in B0 inhomogeneity. By inputting post-exercise B0 values into f, the change in MTRasym due to B0 variation alone was estimated. Thus, the Cr-related post-exercise MTRasym could be isolated and quantified. OXCEST and 31P-MRS were performed in seven subjects across two sessions to compare the OXCEST-derived Cr recovery time constant (TCr) with the ground-truth phosphocreatine recovery time constant (TPCr). ResultsA second-order polynomial function f could reliably describe the relationship between pre-exercise MTRasym and B0 (R2=0.87{+/-}0.07 in the lateral gastrocnemius (LG); R2=0.98{+/-}0.01 in the medial gastrocnemius (MG); R2=0.96{+/-}0.03 in the soleus). The mean pre-exercise MTRasym was approximately 6-7% for all muscle groups. Following exercise, MTRasym increased by 11.4{+/-}4.5% in LG and 8{+/-}2.4% in MG, and showed mono-exponential recovery (R2>0.97). The combined TCr of LG and MG was found to be significantly correlated with TPCr (R{superscript 2}=0.83, p=0.005). ConclusionOXCEST enables reliable assessment of post-exercise Cr recovery and demonstrated strong agreement with 31P-MRS.

bioengineering↗

Generalizability of "GWAS hits" in clinical populations: Lessons from childhood cancer survivors

With mounting interest in translating GWAS hits from large meta-analyses (meta-GWAS) in diverse clinical settings, evaluating their generalizability in target populations is crucial. Here we consider long-term survivors of childhood cancers from the St. Jude Lifetime Cohort Study and show the limited generalizability of 1,376 robust SNP associations reported in the general population across 12 complex anthropometric and cardiometabolic phenotypes (N=2,231; observed-to-expected replication ratio=0.68, P=2.4x10-9). An examination of five comparable phenotypes in a second independent cohort of survivors from the Childhood Cancer Survivor Study corroborated the overall limited generalizability of meta-GWAS hits to survivors (N=4,212, observed-to-expected replication ratio=0.53, P=1.1x10-16). Meta-GWAS hits were less likely to be replicated in survivors exposed to cancer therapies associated with phenotype risk. Examination of complementary DNA methylation data in a subset of survivors revealed that treatment-related methylation patterns at genomic sites linked to meta-GWAS hits may disrupt established genetic signals in survivors.

genetics↗