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

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

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

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

Data_Sheet_2_A zero-dose synthetic baseline for the personalized analysis of [18F]FDG-PET: Application in Alzheimer’s disease.CSV

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

Computed Tomography (CT) Perfusion as an Early Predictive Marker for Treatment Response to Neoadjuvant Chemotherapy in Gastroesophageal Junction Cancer and Gastric Cancer - A Prospective Study

<div><p>Objectives</p><p>To evaluate whether early reductions in CT perfusion parameters predict response to pre-operative chemotherapy prior to surgery for gastroesophageal junction (GEJ) and gastric cancer.</p><p>Materials and Methods</p><p>Twenty-eight patients with adenocarcinoma of the gastro-esophageal junction (GEJ) and stomach were included. Patients received three series of chemotherapy before surgery, each consisting of a 3-week cycle of intravenous epirubicin, cisplatin or oxaliplatin, concomitant with capecitabine peroral. The patients were evaluated with a CT perfusion scan prior to, after the first series of, and after three series of chemotherapy. The CT perfusion scans were performed using a 320-detector row scanner. Tumour volume and perfusion parameters (arterial flow, blood volume and permeability) were computed on a dedicated workstation with a consensus between two radiologists. Response to chemotherapy was evaluated by two measures. Clinical response was defined as a tumour size reduction of more than 50%. Histological response was evaluated based on residual tumour cells in the surgical specimen using the standardized Mandard Score 1 to 5, in which values of 1 and 2 were classified as responders, and 3 to 5 were classified as nonresponders.</p><p>Results</p><p>A decrease in tumour permeability after one series of chemotherapy was positively correlated with clinical response after three series of chemotherapy. Significant changes in permeability and tumour volume were apparent after three series of chemotherapy in both clinical and histological responders. A cut-off value of more than 25% reduction in tumour permeability yielded a sensitivity of 69% and a specificity of 58% for predicting clinical response.</p><p>Conclusion</p><p>Early decrease in permeability is correlated with the likelihood of clinical response to pre-operative chemotherapy in GEJ and gastric cancer. As a single diagnostic test, CT Perfusion only has moderate sensitivity and specificity in response assessment of pre-operative chemotherapy making it insufficient for clinical decision purposes.</p></div

Components of day-to-day variability of cerebral perfusion measurements – Analysis of phase contrast mapping magnetic resonance imaging measurements in healthy volunteers

<div><p>Purpose</p><p>The aim of the study was to investigate the components of day-to-day variability of repeated phase contrast mapping (PCM) magnetic resonance imaging measurements of global cerebral blood flow (gCBF).</p><p>Materials and methods</p><p>Two dataset were analyzed. In Dataset 1 duplicated PCM measurements of total brain flow were performed in 11 healthy young volunteers on two separate days applying a strictly standardized setup. For comparison PCM measurements obtained from a previously published study (Dataset 2) were analyzed in order to assess long-term variability in an aged population in a less strictly controlled setup. Global CBF was calculated by normalizing total brain flow to brain volume. On each day measurements of hemoglobin, caffeine and glucose were obtained. Linear mixed models were applied to estimate coefficients of variation (CV) of total (CV_t), between-subject (CV_b), within-subject day-to-day (CV_w), and intra-session residual variability (CV_r).</p><p>Results</p><p>In Dataset 1 CV_t, CV_b, CV_w and CV_r were estimated to be 11%, 9.4%, 4% and 4.2%, respectively, and to 8.8%, 7.2%, 2.7% and 4.3%, respectively, when adjusting for hemoglobin and plasma caffeine. In Dataset 2 CV_t, CV_b and CV_w were estimated to be 25.4%, 19.2%, and 15.0%, respectively, and decreased to 16.6%, 8.2% and 12.5%, respectively, when adjusting for the same covariates.</p><p>Discussion</p><p>Our results suggest that short-term day-to-day variability of gCBF is relatively low compared to between-subject variability when studied in standardized conditions, whereas long-term variability in an aged population appears to be much larger when studied in less a standardized setup. The results further showed that from 20% to 35% of the total variability in gCBF can be attributed to the effects of hemoglobin and caffeine.</p></div

Datasheet1_Single-voxel delay map from long-axial field-of-view PET scans.docx

ObjectiveWe present an algorithm to estimate the delay between a tissue time activity curve and a blood input curve at a single-voxel level tested on whole-body data from a long-axial field-of-view scanner with tracers of different noise characteristics.MethodsWhole-body scans of 15 patients divided equally among three tracers: [15O]H2O, [18F]FDG and [64Cu]Cu-DOTATATE, were used in development and testing of the algorithm. Delay time were estimated by fitting the cumulatively summed input function and tissue time activity curve with special considerations for noise. To evaluate the performance of the algorithm, it was compared against two other algorithms also commonly applied in delay estimation, name cross-correlation and a one-tissue compartment model with incorporated delay. All algorithms were tested on both synthetic time activity curves produced with the one-tissue compartment model with increasing levels of noise and delays between the tissue activity curve and the blood input curve. Whole-body delay maps were also calculated for each of the three tracers with data acquired on a long-axial field-of-view scanner with high time resolution.ResultsOur proposed model performs better for low signal-to-noise ratio time activity curves compared to both cross-correlation and the one-tissue compartment models for non-[15O]H2O tracers. Testing on synthetically produced time activity curves it displays only a small and even residual delay, while the one-tissue compartment model with included delay showed varying residual delays.ConclusionThe algorithm is robust to noise and proves applicable on a range of tracers as tested on [15O]H2O, [18F]FDG and [64Cu]Cu-DOTATATE, and hence is a viable option offering the ability for delay correction across various organs and tracers in use with kinetic modeling.</p

Pre-operative scan and histological response based on Mandard Score.

<p>Correlation between perfusion parameters pre-operatively and histological response. n = 27.</p