Clinical and genetic features of the Fabry patients.

<p>“+” yes</p><p>“-”no</p><p>*Chaparone-therapy.</p><p>ERT: Enzyme replacement treatment</p><p>Cerebrovascular disease: Infarct or hemorrhage</p><p>Cardiovascular disease: Arrhythmia, congestive heart failure or myocardial infarction</p><p>Renal event: Dialysis (D) or kidney transplantation (KT)</p><p>Unknown: U</p><p>Clinical and genetic features of the Fabry patients.</p

Quantitative 3-dimensional surface projection-analysis of FDG-uptake in patient no 25.

<p>PET-images of patient no. 25 are normalized to whole brain using a database of normal subjects and scaled to Z values from - 4.0 to 4.0 (Neurostat). Projections of Z values are shown onto, respectively, the right and left lateral hemispheric surfaces, the superior and inferior surfaces, and the anterior and posterior surfaces. The uptake in the left cerebellar hemisphere is reduced in addition to uptake in the right frontal cortex. MRI surface projections are presented for anatomical reference in a standard stereotactic space</p

FDG-PET and MRI-features of the Fabry patients.

<p><b><i>n</i>.<i>a</i>.</b><i>not applicable</i></p><p><b><i>-</i></b><i>WML grade 0 or pathology not present</i></p><p><b><i>- / -</i></b><i>no changes in neither PET nor MRI</i></p><p>^<b>a</b> Patient no. 5: symmetrical mildly reduced activity parietotemporally bilaterally</p><p>^<b>b</b> Patient no. 22: symmetrical mildly reduced activity in both thalami <i>Cont</i>.</p><p>^<b>c</b> Progression of pathology on either PET or MRI was detected in the following patients:</p><p>Patient no. 3: PET-study period: seven years</p><p>Patient no. 4: PET-study period: six years.</p><p>Patient no. 8: MRI study period: three years</p><p>Patient no. 9: PET-study period: five years. MRI study period: seven years.</p><p>Patient no. 19: MRI study period: five years</p><p>Patient no. 25: PET/MRI study period: two years.</p><p>FDG-PET and MRI-features of the Fabry patients.</p

PET and MRI of the brain of patient no 25.

<p>Patient no. 25 suffered from a cerebellar hemorrhage and developed a hypometabolic area corresponding to tissue loss in the left cerebellar hemisphere (b + d) in addition to a cerebello-cortical diaschisis (a + b). <b>a</b>: Cortex (MRI fusioned with PET)–decreased activity in the right hemisphere. <b>b</b>: Cerebellum (MRI fusioned with PET)–decreased activity in the left cerebellar hemisphere. <b>c</b>: Cortex (MRI)–no structural changes. <b>d</b>: Cerebellum (MRI)–sequelae after hemorrhage.</p

Data_Sheet_1_A zero-dose synthetic baseline for the personalized analysis of [18F]FDG-PET: Application in Alzheimer’s disease.docx

PurposeBrain 2-Deoxy-2-[18F]fluoroglucose ([18F]FDG-PET) is widely used in the diagnostic workup of Alzheimer’s disease (AD). Current tools for uptake analysis rely on non-personalized templates, which poses a challenge as decreased glucose uptake could reflect neuronal dysfunction, or heterogeneous brain morphology associated with normal aging. Overcoming this, we propose a deep learning method for synthesizing a personalized [18F]FDG-PET baseline from the patient’s own MRI, and showcase its applicability in detecting AD pathology.MethodsWe included [18F]FDG-PET/MRI data from 123 patients of a local cohort and 600 patients from ADNI. A supervised, adversarial model with two connected Generative Adversarial Networks (GANs) was trained on cognitive normal (CN) patients with transfer-learning to generate full synthetic baseline volumes (sbPET) (192 × 192 × 192) which reflect healthy uptake conditioned on brain anatomy. Synthetic accuracy was measured by absolute relative %-difference (Abs%), relative %-difference (RD%), and peak signal-to-noise ratio (PSNR). Lastly, we deployed the sbPET images in a fully personalized method for localizing metabolic abnormalities.ResultsThe model achieved a spatially uniform Abs% of 9.4%, RD% of 0.5%, and a PSNR of 26.3 for CN subjects. The sbPET images conformed to the anatomical information dictated by the MRI and proved robust in presence of atrophy. The personalized abnormality method correctly mapped the pathology of AD subjects while showing little to no anomalies for CN subjects.ConclusionThis work demonstrated the feasibility of synthesizing fully personalized, healthy-appearing [18F]FDG-PET images. Using these, we showcased a promising application in diagnosing AD, and theorized the potential value of sbPET images in other neuroimaging routines.</p

PET/CT images.

<p>Representative [18F]FLT PET/CT images of A2780 (upper panel), A2780/Top216 (mid panel) and SW620 (lower panel) xenografts (dotted circles). [18F]FLT uptake is measured in the same animals at baseline and 6 hours, Day 1 and Day 6 follow treatment initiation with TP202377.</p

Expression of Ki67 and TK1 normalized to expression of reference gene TBP.

<p>Data are presented as fold changes following treatment with Top216/vehicle relative to baseline levels (n = 7 tumors per group). Top216 treatment was initiated at 0 hours and repeated at 48 hours after the first injection. *) P<0.05, **) P<0.01, ***) P<0.001 compared to baseline.</p

Primer and probe sequences for the genes investigated.

<p>Primer and probe sequences for the genes investigated.</p

FDG uptakes after treatment with carboplatin and paclitaxel.

<p>FDG uptake was analyzed one hour post injection in a carboplatin/paclitaxel treatment (n=8 tumors) and a control group (n=5 tumors). The mice were PET/CT scanned at baseline before treatment start and day 1, 4 and 8 after injection of first dose. <b>A</b>) Tumor uptake of FDG during treatment of A2780 xenograft tumors with carboplatin and paclitaxel. Quantitative tumor uptake is presented as SUVmean and SUVmax (mean±SEM). <b>B</b>) Representative PET/CT images of one mouse from the carboplatin and paclitaxel treatment group (upper images) and one mouse from the control vehicle treated group (lower images). Dotted circles indicate the tumors.</p

Fused PET/CT images.

<p>A) The eight images at left are representative coronal fused PET/CT images of two mice scanned with ¹⁸F-FLT at baseline and at 6 hours and 1 and 5 days after treatment start. The images at the top show one mouse treated with Top216 and the images at the bottom show one control mouse which received vehicle. The four images at right show fused PET/CT pictures of two representative mice treated with either Top216 or vehicle and scanned at baseline and 2 hours after treatment initiation. The arrows point towards the tumors. B) Representative coronal fused PET/CT images of two mice scanned with ¹⁸F-FDG at baseline and 6 hours and 1 and 5 days after treatment start. The images at the top show one mouse treated with Top216 and the images at the bottom show one control mouse which received vehicle. The arrows point towards the tumors.</p