Quantitative analysis of PiB-PET with FreeSurfer ROIs

In vivo quantification of β-amyloid deposition using positron emission tomography is emerging as an important procedure for the early diagnosis of the Alzheimer's disease and is likely to play an important role in upcoming clinical trials of disease modifying agents. However, many groups use manually defined regions, which are non-standard across imaging centers. Analyses often are limited to a handful of regions because of the labor-intensive nature of manual region drawing. In this study, we developed an automatic image quantification protocol based on FreeSurfer, an automated whole brain segmentation tool, for quantitative analysis of amyloid images. Standard manual tracing and FreeSurfer-based analyses were performed in 77 participants including 67 cognitively normal individuals and 10 individuals with early Alzheimer's disease. The manual and FreeSurfer approaches yielded nearly identical estimates of amyloid burden (intraclass correlation = 0.98) as assessed by the mean cortical binding potential. An MRI test-retest study demonstrated excellent reliability of FreeSurfer based regional amyloid burden measurements. The FreeSurfer-based analysis also revealed that the majority of cerebral cortical regions accumulate amyloid in parallel, with slope of accumulation being the primary difference between regions

CTNI-53. RADIATION TREATMENT VOLUMES BEFORE AND AFTER BRAF/MEK THERAPY IN NEWLY DIAGNOSED PAPILLARY CRANIOPHARYNGIOMAS: A CORRELATIVE ANALYSIS OF THE ALLIANCE A071601 PHASE II TRIAL

Abstract PURPOSE Standard of care for craniopharyngiomas is surgery with or without radiotherapy (RT). Cohort A of Alliance A071601 evaluated the efficacy of BRAF/MEK inhibition with vemurafenib/cobimetinib in patients with previously untreated papillary craniopharyngiomas (PCP), which carry the BRAF V600E mutation. Cohort B is currently enrolling patients with recurrence after RT. In a correlative analysis, we examined changes in RT volumes after BRAF/MEK therapy in Cohort A. METHODS Previously unirradiated patients with BRAF-mutated PCP were treated with vemurafenib/cobimetinib. Sixteen patients had scans available before starting vemurafenib/cobimetinib (“pre-therapy”) and after completing therapy (“post-therapy”). Two patients went off study treatment after 8 and 9 days due to side-effects and were excluded for this analysis. Gross target volumes (GTV) were contoured on pre-therapy and post-therapy scans. On post-therapy scans, an additional target comprising gross disease and at-risk regions for microscopic residual disease (GTV-micro) was defined and considered the treatment volume. Clinical target volume (CTV) was a 5-mm uniform expansion on pre-therapy GTV and post-therapy GTV-micro. Volumes were independently reviewed by two radiation oncologists. Changes in volumes from pre- versus post-therapy were compared using the Wilcoxon signed rank test. RESULTS In 14 patients evaluated, 57% were female and median age at enrollment was 49.5 years (range 33-83). Median time on treatment was 8.9 months (range 4.0-18.0). Median GTV pre-therapy was 3.8 mL (range 0.2-23.4) versus 0.3 mL (range 0.0-3.2) post-therapy (p=0.0001) and 1.7 mL (range 0.1-8.0) post-therapy GTV-micro (p=0.0001). Median CTV pre-therapy was 13.7 mL (range 2.8-51.8) versus 9.1 mL (range 2.2-27.5) post-therapy (p=0.0001). All tumors abutted the optic chiasm pre-therapy, only 6 did post-therapy. CONCLUSIONS Vemurafenib/cobimetinib resulted in smaller RT volumes. BRAF/MEK inhibitors could reduce RT volumes and spare dose to surrounding normal structures. Enrollment to Cohort B of Alliance A071601 should be considered for patients with recurrent tumors after RT. SUPPORT https://acknowledgments.alliancefound.or

Correlations of binding potentials between raw measurements and partial volume corrected measurements for selected FreeSurfer regions and MCBP in G1.

<p>Also listed were the slope and intercept of the linear fitting between raw measurements and partial volume corrected ones. All the correlations were statistically significant (p<10⁻⁶), correction for multiple comparison was not performed.</p

Correlations of cortical regions binding potentials to MCBP and to their corresponding white matter regions in G1.

<p>All the correlations were statistically significant (p<10⁻⁶), correction for multiple comparison was not performed.</p

Test-retest reliability of FreeSurfer based PiB quantification in G2.

<p>Test-retest reliability of FreeSurfer based PiB quantification in G2.</p

Example of regions-of-interest (ROI) defined manually on one of individual.

<p>Example of regions-of-interest (ROI) defined manually on one of individual.</p

Correlation of binding potentials to MCBP for subcortical structures (G1).

<p>Correlation of binding potentials to MCBP for subcortical structures (G1).</p

List of regions that have less than 10% difference in classifications for PiB positivity, and their corresponding BP_ND threshold, number of difference in classifications (NOD), and percentage difference in classification.

<p>List of regions that have less than 10% difference in classifications for PiB positivity, and their corresponding BP_ND threshold, number of difference in classifications (NOD), and percentage difference in classification.</p

Scatter plot of MCBP values obtained using manually and FreeSurfer defined ROIs (previously shown in [47]).

<p>Scatter plot of MCBP values obtained using manually and FreeSurfer defined ROIs (previously shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073377#pone.0073377-Illarioshkin1" target="_blank">[47]</a>).</p