Automatic brain tumor classification by MRS has been under development for more than a decade. Nonetheless, to our knowledge, there are no published evaluations of predictive models with unseen cases that are subsequently acquired in different centers. The multicenter eTUMOUR project (2004–2009), which builds upon previous expertise from the INTERPRET project (2000–2002) has allowed such an evaluation to take place. A total of 253 pairwise classifiers for glioblastoma, meningioma, metastasis, and low-grade glial diagnosis were inferred based on 211 SV short TE INTERPRET MR spectra obtained at 1.5 T (PRESS or STEAM, 20–32 ms) and automatically pre-processed. Afterwards, the classifiers were tested with 97 spectra, which were subsequently compiled during eTUMOUR. In our results based on subsequently acquired spectra, accuracies of around 90% were achieved for most of the pairwise discrimination problems. The exception was for the glioblastoma versus metastasis discrimination, which was below 78%. A more clear definition of metastases may be obtained by other approaches, such as MRSI + MRI. The prediction of the tumor type of in-vivo MRS is possible using classifiers developed from previously acquired data, in different hospitals with different instrumentation under the same acquisition protocols. This methodology may find application for assisting in the diagnosis of new brain tumor cases and for the quality control of multicenter MRS databases.
Lower levels of N‐acetylaspartate (NAA), a marker of axonal damage, have been found in the normal‐appearing white matter (NAWM) of relapsing‐remitting multiple sclerosis (RRMS) patients with low physical disability. However, its relation to the clinical status of these patients remains unclear. We explored the association between NAA levels [normalized to creatine (Cr), NAA/Cr] and a cognitive feature that is not measured by the standard scales that address functional disability [e.g. Expanded Disability Scale Score (EDSS)] in early RRMS. Given that a considerable number of RRMS patients present attentional dysfunction early in the disease and assuming a functional‐anatomical oriented guide, it was hypothesized that patients with worse attentional performance would show lower NAWM NAA/Cr values in the locus coeruleus nuclei of the pontine ascendant reticular activating system. Proton magnetic resonance spectroscopy (1H‐MRS) examinations with concurrent clinical evaluation were acquired for 19 RRMS patients with a mean evolution time of 24 months (range 10–60) and mild disability (EDSS 0–3.5, median = 1). 1H‐MRS was obtained with spectroscopic imaging and measures were taken from the right and left hemipons. Attention was measured by means of the dichotic listening (DL) paradigm to increase the sensitivity of the testing to subtle attentional deficits. A consonant‐vowel DL test was measured with and without attentional instructions. For the attentional condition, the test was digitally manipulated to cue automatically to the ear to be attended, thus allowing the obtention of both a linguistic lateralization index (LI) and an index of integrity of attentional shifts (ASI). Attentional impairment was demonstrated in 47.3% of the patients. Pontine NAA/Cr levels accounted for 39% of the ASI variability (β = 0.65, P < 0.002) but did not relate to the LI. Moreover, when NAA/Cr levels were considered separately as left and right hemipons values in a multivariate stepwise linear regression model, the right NAA/Cr ratio alone explained 43% of the ASI variability (β = 0.68, P < 0.001). Since the RRMS patients with greater attentional disturbances exhibited the lowest NAA/Cr levels, it is concluded that NAA provides a specific measure of pathological changes that are also relevant for cognitive functions. The use of both 1H‐MRS and DL showed the connection between axonal damage at right locus coeruleus and auditive selective attention dysfunction in early‐stage RRMS.
Non Muscle Invasive Bladder Cancer (NMIBC) is among the most frequent malignant cancers worldwide. NMIBC is treated by transurethral resection of the bladder tumor (TURBT) and intravesical therapies, and has the highest recurrence rate among solid tumors. It requires a lifelong patient monitoring based on repeated cystoscopy and urinary cytology, both having drawbacks that include lack of sensitivity and specificity, invasiveness and care costs. We conducted an investigative clinical study to examine changes in the urinary metabolome of NMBIC patients before and after TURBT, as well during the subsequent surveillance period. Adjusting by prior probability of recurrence per risk, discriminant analysis of UPLC-MS metabolic profiles, displayed negative predictive values for low, low-intermediate, high-intermediate and high risk patient groups of 96.5%, 94.0%, 92.9% and 76.1% respectively. Detailed analysis of the metabolome revealed several candidate metabolites and perturbed phenylalanine, arginine, proline and tryptophan metabolisms as putative biomarkers. A pilot retrospective analysis of longitudinal trajectories of a BC metabolic biomarkers during post TURBT surveillance was carried out and the results give strong support for the clinical use of metabolomic profiling in assessing NMIBC recurrence.