68Ga-RM2 PET-MRI versus MRI alone for evaluation of patients with biochemical recurrence of prostate cancer: a single-centre, single-arm, phase 2/3 imaging trial.

BACKGROUND: National Comprehensive Cancer Network guidelines include prostate-specific membrane antigen (PSMA)-targeted PET for detection of biochemical recurrence of prostate cancer. However, targeting a single tumour characteristic might not be sufficient to reflect the full extent of disease. Gastrin releasing peptide receptors (GRPR) have been shown to be overexpressed in prostate cancer. In this study, we aimed to evaluate the diagnostic performance of the GRPR-targeting radiopharmaceutical 68Ga-RM2 in patients with biochemical recurrence of prostate cancer. METHODS: This single-centre, single-arm, phase 2/3 trial was done at Stanford University (USA). Adult patients (aged ≥18 years) with biochemical recurrence of prostate cancer, a Karnofsky performance status of 50 or higher, increasing prostate-specific antigen concentration 0·2 ng/mL or more after prostatectomy or 2 ng/mL or more above nadir after radiotherapy, and non-contributory conventional imaging (negative CT or MRI, and bone scan) were eligible. All participants underwent 68Ga-RM2 PET-MRI. The primary outcome was the proportion of patients with PET-positive findings on 68Ga-RM2 PET-MRI compared with MRI alone after initial therapy, at a per-patient and per-lesion level. The primary outcome would be considered met if at least 30% of patients had one or more lesions detected by 68Ga-RM2 PET-MRI and the detection by 68Ga-RM2 PET-MRI was significantly greater than for MRI. Each PET scan was interpreted by three independent masked readers using a standardised evaluation criteria. This study is registered with ClinicalTrials.gov, NCT02624518, and is complete. FINDINGS: Between Dec 12, 2015, and July 27, 2021, 209 men were screened for eligibility, of whom 100 were included in analyses. Median follow-up was 49·3 months (IQR 36·7-59·2). The primary endpoint was met; 68Ga-RM2 PET-MRI was positive in 69 (69%) patients and MRI alone was positive in 40 (40%) patients (p<0·0001). In the per-lesion analysis 68Ga-RM2 PET-MRI showed significantly higher detection rates than MRI alone (143 vs 96 lesions; p<0·0001). No grade 1 or worse events were reported. INTERPRETATION: 68Ga-RM2 PET-MRI showed better diagnostic performance than MRI alone in patients with biochemical recurrence of prostate cancer. Further prospective comparative studies with PSMA-targeted PET are needed to gain a better understanding of GRPR and PSMA expression patterns in these patients. FUNDING: The US Department of Defense.

Same-day post-therapy imaging with a new generation whole-body digital SPECT/CT in assessing treatment response to [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer.

PURPOSE: Lutetium-177 [177Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24 h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [177Lu]Lu-PSMA-617. METHODS: In this retrospective study, 68 men with progressive mCRPC treated with [177Lu]Lu-PSMA-617 at our center from June 2022 to June 2023 were evaluated. Digital whole-body SPECT/CT imaging was performed after [177Lu]Lu-PSMA-617infusion (mean ± SD: 1.8 ± 0.6 h, range 1.1-4.9 h). Quantitative analysis of [177Lu]Lu-PSMA-617 positive lesions was performed in patients who underwent at least 2 post-therapy SPECT/CT, using liver parenchyma uptake as reference. Metrics including [177Lu]Lu-PSMA-617 positive total tumor volume (Lu-TTV), SUVmax and SUVmean were calculated. These quantitative metrics on post-infusion SPECT/CT images after cycles 1, 2 and 3 were correlated with overall survival (OS), prostate specific antigen-progression free survival (PSA-PFS) as defined by prostate cancer working group 3 (PCWG3), and PSA decrease over 50% (PSA50) response rates. RESULTS: 56 patients (means age 76.2 ± 8.1 years, range: 60-93) who underwent at least 2 post-therapy SPECT/CT were included in the image analysis. The whole-body SPECT/CT scans (~ 12 min per scan) were well tolerated, with 221 same-day scans performed (89%). At a median of 10-months follow-up, 33 (58.9%) patients achieved PSA50 after [177Lu]Lu-PSMA-617 treatment and median PSA-PFS was 5.0 months (range: 1.0-15 months) while median OS was not reached. Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had > 30% reduction in Lu-TTV, associated with significantly improved overall survival (median not reached vs. 6 months, P = 0.008) and PSA-PFS (median 6 months vs. 1 months, P < 0.001). However, changes in SUVmax or SUVmean did not correlate with PSA-PFS or OS. CONCLUSION: We successfully implemented same-day post-therapy SPECT/CT after [177Lu]Lu-PSMA-617 infusions. Quantitation of 1-2 h post-therapy SPECT/CT images is a promising method for assessing treatment response. However, the approach is currently limited by its suboptimal detection of small tumor lesions and the necessity of incorporating a third-cycle SPECT/CT to mitigate the effects of any potential treatment-related flare-up. Further investigation in a larger patient cohort and prospective validation is essential to confirm these findings and to explore the role of SPECT/CT as a potential adjunct to PSMA PET/CT in managing mCRPC.

Predicting FDG-PET Images From Multi-Contrast MRI Using Deep Learning in Patients With Brain Neoplasms.

BACKGROUND: 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is valuable for determining presence of viable tumor, but is limited by geographical restrictions, radiation exposure, and high cost. PURPOSE: To generate diagnostic-quality PET equivalent imaging for patients with brain neoplasms by deep learning with multi-contrast MRI. STUDY TYPE: Retrospective. SUBJECTS: Patients (59 studies from 51 subjects; age 56 ± 13 years; 29 males) who underwent 18 F-FDG PET and MRI for determining recurrent brain tumor. FIELD STRENGTH/SEQUENCE: 3T; 3D GRE T1, 3D GRE T1c, 3D FSE T2-FLAIR, and 3D FSE ASL, 18 F-FDG PET imaging. ASSESSMENT: Convolutional neural networks were trained using four MRIs as inputs and acquired FDG PET images as output. The agreement between the acquired and synthesized PET was evaluated by quality metrics and Bland-Altman plots for standardized uptake value ratio. Three physicians scored image quality on a 5-point scale, with score ≥3 as high-quality. They assessed the lesions on a 5-point scale, which was binarized to analyze diagnostic consistency of the synthesized PET compared to the acquired PET. STATISTICAL TESTS: The agreement in ratings between the acquired and synthesized PET were tested with Gwet's AC and exact Bowker test of symmetry. Agreement of the readers was assessed by Gwet's AC. P = 0.05 was used as the cutoff for statistical significance. RESULTS: The synthesized PET visually resembled the acquired PET and showed significant improvement in quality metrics (+21.7% on PSNR, +22.2% on SSIM, -31.8% on RSME) compared with ASL. A total of 49.7% of the synthesized PET were considered as high-quality compared to 73.4% of the acquired PET which was statistically significant, but with distinct variability between readers. For the positive/negative lesion assessment, the synthesized PET had an accuracy of 87% but had a tendency to overcall. CONCLUSION: The proposed deep learning model has the potential of synthesizing diagnostic quality FDG PET images without the use of radiotracers. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Modified PROMISE criteria for standardized interpretation of gastrin-releasing peptide receptor (GRPR)-targeted PET.

PURPOSE: There are image interpretation criteria to standardize reporting prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET). As up to 10% of prostate cancer (PC) do not express PSMA, other targets such as gastrin-releasing peptide receptor (GRPR) are evaluated. Research on GRPR-targeted imaging has been slowly increasing in usage at staging and biochemical recurrence (BCR) of PC. We therefore propose a modification of the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria (mPROMISE) for GRPR-targeted PET. METHODS: [68 Ga]Ga-RM2 PET data from initially prospective studies performed at our institution were retrospectively reviewed: 44 patients were imaged for staging and 100 patients for BCR PC. Two nuclear medicine physicians independently evaluated PET according to the mPROMISE criteria. A third expert reader served as standard reference. Interreader reliability was computed for GRPR expression, prostate bed (T), lymph node (N), skeleton (Mb), organ (Mc) metastases, and final judgment of the scan. RESULTS: The interrater reliability for GRPR PET at staging was moderate for GRPR expression (0.59; 95% confidence interval [CI] 0.40, 0.78), substantial for T-stage (0.78; 95% CI 0.63, 0.94), and almost perfect for N-stage (0.97; 95% CI 0.92, 1.00) and final judgment (0.92; 95% CI 0.82, 1.00). The interreader agreement at BCR showed substantial agreement for GRPR expression (0.70; 95% CI 0.59, 0.81) and final judgment (0.65; 95% CI 0.53, 0.78), while almost perfect agreement was seen across the major categories (T, N, Mb, Mc). Acceptable performance of the mPROMISE criteria was found for all subsets when compared to the standard reference. CONCLUSION: Interpreting GRPR-targeted PET using the mPROMISE criteria showed its reliability with substantial or almost perfect interrater agreement across all major categories. The proposed modification of the PROMISE criteria will aid clinicians in decreasing the level of uncertainty, and clinical trials to achieve uniform evaluation, reporting, and comparability of GRPR-targeted PET. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03113617 and NCT02624518.

SPECT at the speed of PET: a feasibility study of CZT-based whole-body SPECT/CT in the post 177Lu-DOTATATE and 177Lu-PSMA617 setting.

PURPOSE: To evaluate the feasibility of using the StarGuide (General Electric Healthcare, Haifa, Israel), a new generation multi-detector cadmium-zinc-telluride (CZT)-based SPECT/CT, for whole-body imaging in the setting of post-therapy imaging of 177Lu-labeled radiopharmaceuticals. METHODS: Thirty-one patients (34-89 years old; mean ± SD, 65.5 ± 12.1) who were treated with either 177Lu-DOTATATE (n=17) or 177Lu-PSMA617 (n=14) as part of standard of care were scanned post-therapy with the StarGuide; some were also scanned with the standard GE Discovery 670 Pro SPECT/CT. All patients had either 64Cu-DOTATATE or 18F-DCFPyL PET/CT prior to first cycle of therapy for eligibility check. The detection/targeting rate (lesion uptake greater than blood pool uptake) of large lesions meeting RECIST 1.1 size criteria on post-therapy StarGuide SPECT/CT was evaluated and compared to the standard design GE Discovery 670 Pro SPECT/CT (when available) and pre-therapy PET by two nuclear medicine physicians with consensus read. RESULTS: This retrospective analysis identified a total of 50 post-therapy scans performed with the new imaging protocol from November 2021 to August 2022. The StarGuide system acquired vertex to mid-thighs post-therapy SPECT/CT scans with 4 bed positions, 3 min/bed and a total scan time of 12 min. In comparison, the standard GE Discovery 670 Pro SPECT/CT system typically acquires images in 2 bed positions covering the chest, abdomen, and pelvis with a total scan time of 32 min. The pre-therapy 64Cu-DOTATATE PET takes 20 min with 4 bed positions on GE Discovery MI PET/CT, and 18F-DCFPyL PET takes 8-10 min with 4-5 bed positions on GE Discovery MI PET/CT. This preliminary evaluation showed that the post-therapy scans acquired with faster scanning time using StarGuide system had comparable detection/targeting rate compared to the Discovery 670 Pro SPECT/CT system and detected large lesions defined by RECIST criteria on the pre-therapy PET scans. CONCLUSION: Fast acquisition of whole-body post-therapy SPECT/CT is feasible with the new StarGuide system. Short scanning time improves the patients' clinical experience and compliance which may lead to increased adoption of post-therapy SPECT. This opens the possibility to offer imaged-based treatment response assessment and personalized dosimetry to patients referred for targeted radionuclide therapies.

Validity of age estimation methods and reproducibility of bone/dental maturity indices for chronological age estimation.

AIM: This systematic review sought to assess the validity of age estimation methods based on bone or dental maturity indices and their reproducibility through a meta-analysis of validation and reproducibility studies. DATA SOURCES: A systematic online search was conducted in PubMed and Google Scholar. STUDY SELECTION: Cross-sectional studies were included. The authors excluded articles without information on validity and reproducibility outcomes, articles not written in English or Italian, and those where it was impossible to obtain pooled reproducibility estimates of Cohen's kappa or the intraclass correlation coefficient (ICC) due to a lack of information on the variability measure. DATA EXTRACTION AND SYNTHESIS: The authors tried to follow the preferred reporting items for systematic reviews and meta-analyses (PRISMA) protocol. They also considered the PICOS/PECOS strategy to assess the research questions in their included studies; nevertheless, no particular guideline was reported to be consistently followed in their study. RESULTS: Twenty-three (23) studies were selected for data extraction and critical appraisal. The pooled male mean error of the age prediction was 0.08 years (95% CI: -0.12; 0.29), and the pooled female mean error was 0.09 years (95% CI: -0.12; 0.30). Studies using Nolla's method had a mean error closest to zero with a slight overestimation: mean male age prediction error of 0.02 (95% CI: -0.37; 0.41) and mean female age prediction error of 0.03 (95% CI: -0.34; 0.41). Haavikko's method had a mean error of -1.12 (95% CI: -2.29; 0.06) and -1.33 (95% CI: -2.54; -0.13) for males and females, respectively. Cameriere's method also underestimated the chronological age and was the only method with a higher absolute mean error for males than females (males: -0.22 [95% CI: -0.44; 0.00]; females: -0.17 [95% CI: -0.34; -0.01]). Overall, Demirjian's and Willems's methods tended to overestimate chronological age in both males (Demirjian: 0.59 [95% CI: 0.28; 0.91]; Willems: 0.07 [95% CI: -0.17; 0.31]) and females (Demirjian: 0.64 [95% CI 0.38; 0.90]; Willems: 0.09 [95% CI: -0.13; 0.31]). The prediction intervals (PI) overlapped zero for all methods, rendering the difference between estimated and chronological ages not statistically significant for males and females. Cameriere's method showed the smallest PI for both biological genders, while the Haavikko and other methods had the widest intervals. No heterogeneity was observed in inter-examiner (heterogeneity: Q = 5.78, p = 0.888) and intra-examiner (heterogeneity: Q = 9.11, p = 0.611) agreement, so a fixed-effects model was used. For inter-examiner agreement, the ICC ranged from 0.89 to 0.99, and the meta-analytic pooled ICC was 0.98 (95% CI 0.97; 1.00), which was near-perfect reliability. Concerning intra-examiner agreement, the ICCs ranged from 0.90 to 1.00, and the meta-analytic pooled ICC was 0.99 (95% CI 0.98; 1.00), which was also close to perfect reliability. CONCLUSIONS: This study recommended the Nolla and Cameriere methods as preferred approaches while mentioning that the Cameriere method was validated on a smaller sample size than Nolla's, thus requiring further testing on additional populations to better assess the mean error estimates by sex. However, the evidence in this paper is of very low quality and offers no certainty.

Optimum PZT Patch Size for Corrosion Detection in Reinforced Concrete Using the Electromechanical Impedance Technique.

This paper proposes the use of a 1-dimensional (1-D) electromechanical impedance model to extract proper design guidelines when selecting patch-size and frequency range for corrosion detection in reinforced concrete structures using the electromechanical impedance (EMI) technique. The theoretical results show that the sensitivity mainly lies in the peak frequencies of the impedance spectrum, while outside resonant frequencies the sensitivity levels are low, and are prone to natural variation. If the mechanical impedance ratio between the host structure and patch is too large, the peaks and thereby the sensitivity decreases. This can be counteracted by increasing the patch thickness. Tests were carried out in reinforced concrete structures, where lead zirconate titanate (PZT) patches were attached to the rebars. Patches measuring 10 × 10 mm in length and width, with thicknesses of 0.3, 0.5 and 1.5 mm, were used. The results show that only the 10 × 10 × 1.5 mm patch, was able to generate a clear peak in the 50 kHz to 400 kHz impedance spectrum. Furthermore, a reinforced concrete structure with the 1.5 mm patch attached was induced significant corrosion damages, resulting in cracking of the structure. Due to this, a leftward shift of the main peak, and creation of new peaks in the spectrum was observed.

Quantification of brain oxygen extraction and metabolism with [15O]-gas PET: A technical review in the era of PET/MRI.

Oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2) are key cerebral physiological parameters to identify at-risk cerebrovascular patients and understand brain health and function. PET imaging with [15O]-oxygen tracers, either through continuous or bolus inhalation, provides non-invasive assessment of OEF and CMRO2. Numerous tracer delivery, PET acquisition, and kinetic modeling approaches have been adopted to map brain oxygenation. The purpose of this technical review is to critically evaluate different methods for [15O]-gas PET and its impact on the accuracy and reproducibility of OEF and CMRO2 measurements. We perform a meta-analysis of brain oxygenation PET studies in healthy volunteers and compare between continuous and bolus inhalation techniques. We also describe OEF metrics that have been used to detect hemodynamic impairment in cerebrovascular disease. For these patients, advanced techniques to accelerate the PET scans and potential synthesis with MRI to avoid arterial blood sampling would facilitate broader use of [15O]-oxygen PET for brain physiological assessment.

Prognostic value of volumetric PET parameters at early response evaluation in melanoma patients treated with immunotherapy.

PURPOSE: The purpose of this study was to investigate the prognostic value of whole-body metabolic tumor volume (MTV) and other metabolic tumor parameters, obtained from baseline and first restaging 18F-FDG PET/CT scans in melanoma patients treated with immune checkpoint inhibitors (ICIs). METHODS: Eighty-five consecutive melanoma patients (M, 57; F, 28) treated with ICIs who underwent PET/CT scans before and approximately 3 months after the start of immunotherapy were retrospectively enrolled. Metabolic tumor parameters including MTV for all melanoma lesions were measured on each scan. A Cox proportional hazards model was used for univariate and multivariate analyses of metabolic parameters combined with known clinical prognostic factors associated with overall survival (OS). Kaplan-Meier curves for patients dichotomized based on median values of imaging parameters were generated. RESULTS: The median OS time in all patients was 45 months (95% CI 24-45 months). Univariate analysis demonstrated that MTV obtained from first restaging PET/CT scans (MTVpost) was the strongest prognostic factor for OS among PET/CT parameters (P < 0.0001). The median OS in patients with high MTVpost (≥ 23.44) was 16 months (95% CI 12-32 months) as compared with more than 60 months in patients with low MTVpost (< 23.44) (P = 0.0003). A multivariate model including PET/CT parameters and known clinical prognostic factors revealed that MTVpost and the presence of central nervous system lesions were independent prognostic factors for OS (P = 0.0004, 0.0167, respectively). One pseudoprogression case (1.2%) was seen in this population and classified into the high MTVpost group. CONCLUSION: Whole-body metabolic tumor volume from PET scan acquired approximately 3 months following initiation of immunotherapy (MTVpost) is a strong prognostic indicator of OS in melanoma patients. Although the possibility of pseudoprogression must be considered whenever evaluating first restaging PET imaging, it only occurred in 1 patient in our cohort.

Patient Selection and Toxicities of PRRT for Metastatic Neuroendocrine Tumors and Research Opportunities.

OPINION STATEMENT: Neuroendocrine tumors (NETs) are a heterogenous group of neoplasms characterized by varied biological hallmarks and behavior, ranging from indolent to aggressive. For many decades, somatostatin analogues and few targeted therapies were available for NETs and these therapies had minimal response rates. However, there have been a number of recent treatment advances. Peptide receptor radionuclide therapy (PRRT) is a novel approach to treatment of NETs and has changed the landscape of treatment for NETs. It is a form of targeted therapy in which a radiolabeled somatostatin analogue delivers radiation specifically to tumor cells expressing the somatostatin receptor.

Perfusion Scintigraphy in Diagnosis and Management of Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication of acute pulmonary embolism (PE). Because the treatment of CTEPH is markedly different from that of other types of pulmonary hypertension, lung ventilation-perfusion (V/Q) scintigraphy is recommended for the workup of patients with unexplained pulmonary hypertension. Lung V/Q scintigraphy is superior to CT pulmonary angiography for detecting CTEPH. Perfusion defect findings of CTEPH can be different from those of acute PE. Familiarity with the patterns of perfusion defects seen during the initial workup of CTEPH and the expected posttreatment changes seen at follow-up imaging is essential for accurate interpretation of V/Q scintigraphy findings. ©RSNA, 2019.

Prospective Comparison of 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI in Patients with Biochemically Recurrent Prostate Cancer.

Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors are both overexpressed in prostate cancer (PC) but may provide complementary information.68Ga-PSMA-R2 and 68Ga-NeoB (DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-NH-CH[CH2-CH(CH3)2]2) are novel PET radiopharmaceuticals that were developed for theranostic use. In this phase II imaging study, we assessed the feasibility, safety, and diagnostic performance of 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI for detection of biochemically recurrent PC. Methods: We prospectively enrolled 27 men with suspected biochemically recurrent PC after initial treatment but noncontributory conventional imaging results (negative or equivocal findings on MRI, CT, and/or bone scan). Participants underwent 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI within 2 wk in noncontrolled order. The SUVmax of putative PC lesions was measured and compared with a composite reference standard (histopathology, follow-up imaging, prostate-specific antigen change). The SUVmax and SUVmean of background organs were measured. Vital signs were recorded before injection of the radiopharmaceuticals and after the scans. Adverse events were recorded up to 72 h after each scan. Results: The prostate-specific antigen level at enrollment was 3.5 ± 3.9 ng/mL (range, 0.3-13.5 ng/mL). 68Ga-NeoB PET/MRI detected 31 lesions in 18 patients (66.7%), whereas 68Ga-PSMA-R2 identified 20 lesions in 15 participants (55.6%). 68Ga-NeoB PET/MRI showed higher sensitivity (85.7% vs. 71.4%), accuracy (88.9% vs. 77.8%), and negative predictive value (66.7% vs. 50.0%) than 68Ga-PSMA-R2, whereas specificity and positive predictive value were equally high (100.0% for both). In 6 patients, 68Ga-NeoB PET/MRI identified 14 lesions that were false-negative on 68Ga-PSMA-R2 PET/MRI. The mean lesion SUVmax was 6.6 ± 3.2 (range, 2.9-13.2) for 68Ga-NeoB and 4.4 ± 1.5 (range, 2.6-8.8) for 68Ga-PSMA-R2 (P = 0.019). Overall lower uptake was noted in tumors and background organs for 68Ga-PSMA-R2. There were no significant changes in vital signs before and after the scans. No adverse events were reported in the 72-h period after scans. Conclusion: 68Ga-NeoB and 68Ga-PSMA-R2 are safe for diagnostic imaging. 68Ga-NeoB PET/MRI showed better diagnostic performance than 68Ga-PSMA-R2. 68Ga-PSMA-R2 showed overall lower uptake, equally in background organs and tumors, and might therefore not be an ideal theranostic compound. Further evaluation in larger cohorts is needed to confirm our preliminary data.

Temperature effect on a weighted vortex spin-torque nano-oscillator for neuromorphic computing.

In this work, we present fabricated magnetic tunnel junctions (MTJs) that can serve as magnetic memories (MMs) or vortex spin-torque nano-oscillators (STNOs) depending on the device geometry. We explore the heating effect on the devices to study how the performance of a neuromorphic computing system (NCS) consisting of MMs and STNOs can be enhanced by temperature. We further applied a neural network for waveform classification applications. The resistance of MMs represents the synaptic weights of the NCS, while temperature acts as an extra degree of freedom in changing the weights and TMR, as their anti-parallel resistance is temperature sensitive, and parallel resistance is temperature independent. Given the advantage of using heat for such a network, we envision using a vertical-cavity surface-emitting laser (VCSEL) to selectively heat MMs and/or STNO when needed. We found that when heating MMs only, STNO only, or both MMs and STNO, from 25 to 75 °C, the output power of the STNO increases by 24.7%, 72%, and 92.3%, respectively. Our study shows that temperature can be used to improve the output power of neural networks, and we intend to pave the way for future implementation of a low-area and high-speed VCSEL-assisted spintronic NCS.

Adaptation of cerebral oxygen metabolism and blood flow and modulation of neurovascular coupling with prolonged stimulation in human visual cortex.

Prolonged visual stimulation results in neurophysiologic and hemodynamic adaptation. However, the hemodynamic adaptation appears to be small compared to neural adaptation. It is not clear how the cerebral metabolic rate of oxygen (CMRO2) is affected by adaptation. We measured cerebral blood flow (CBF) and CMRO2 change in responses to peripheral stimulation either continuously, or intermittently (on/off cycles). A linear system's response to the continuous input should be equal to the sum of the original response to the intermittent input and a version of that response shifted by half a cycle. The CMRO2 response showed a large non-linearity consistent with adaptation, the CBF response adapted to a lesser degree, and the blood oxygenation level dependent (BOLD) response was nearly linear. The metabolic response was coupled with a larger flow in the continuous condition than in the intermittent condition. Our results suggest that contrast adaptation improves energy economy of visual processing. However BOLD modulations may not accurately represent the underlying metabolic nonlinearity due to modulation of the coupling of blood flow and oxygen metabolism changes.

Luminance contrast of a visual stimulus modulates the BOLD response more than the cerebral blood flow response in the human brain.

The blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI) depends on the evoked changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) in response to changes in neural activity. This response is strongly modulated by the CBF/CMRO(2) coupling relationship with activation, defined as n, the ratio of the fractional changes. The reliability of the BOLD signal as a quantitative reflection of underlying physiological changes depends on the stability of n in response to different stimuli. The effect of visual stimulus contrast on this coupling ratio was tested in 9 healthy human subjects, measuring CBF and BOLD responses to a flickering checkerboard at four visual contrast levels. The theory of the BOLD effect makes a robust prediction-independent of details of the model-that if the CBF/CMRO(2) coupling ratio n remains constant, then the response ratio between the lowest and highest contrast levels should be higher for the BOLD response than the CBF response because of the ceiling effect on the BOLD response. Instead, this response ratio was significantly lower for the BOLD response (BOLD response: 0.23 ± 0.13, mean ± SD; CBF response: 0.42 ± 0.18; p=0.0054). This data is consistent with a reduced dynamic range (strongest/weakest response ratio) of the CMRO(2) response (~1.7-fold) compared to that of the CBF response (~2.4-fold) as luminance contrast increases, corresponding to an increase of n from 1.7 at the lowest contrast level to 2.3 at the highest contrast level. The implication of these results for fMRI studies is that the magnitude of the BOLD response does not accurately reflect the magnitude of underlying physiological processes.

Retroperitoneal Inflammation Detected on FDG PET/CT in Patient on Long-Term Immunotherapy.

ABSTRACT: A 68-year-old man with a history of pulmonary adenocarcinoma on maintenance pembrolizumab presented for surveillance imaging. 18 F-FDG PET/CT demonstrated new ill-defined right retroperitoneal and presacral soft tissue stranding with associated FDG uptake suggestive of inflammation. Biopsy results revealed fibroadipose tissue with extensive lymphoplasmacytic inflammation concerning for immunotherapy-related toxicity. The patient was subsequently taken off pembrolizumab, which he had been on for approximately 3 years. Recognition of immunotherapy-related adverse effects and how they can manifest on 18 F-FDG PET/CT is important for prompt cessation of treatment.

NET-TEN: a silicon neuromorphic network for low-latency detection of seizures in local field potentials.

Objective. Therapeutic intervention in neurological disorders still relies heavily on pharmacological solutions, while the treatment of patients with drug resistance remains an unresolved issue. This is particularly true for patients with epilepsy, 30% of whom are refractory to medications. Implantable devices for chronic recording and electrical modulation of brain activity have proved a viable alternative in such cases. To operate, the device should detect the relevant electrographic biomarkers from local field potentials (LFPs) and determine the right time for stimulation. To enable timely interventions, the ideal device should attain biomarker detection with low latency while operating under low power consumption to prolong battery life.Approach. Here we introduce a fully-analog neuromorphic device implemented in CMOS technology for analyzing LFP signals in anin vitromodel of acute ictogenesis. Neuromorphic networks have progressively gained a reputation as low-latency low-power computing systems, which makes them a promising candidate as processing core of next-generation implantable neural interfaces.Main results. The developed system can detect ictal and interictal events with ms-latency and with high precision, consuming on average 3.50 nW during the task.Significance. The work presented in this paper paves the way to a new generation of brain implantable devices for personalized closed-loop stimulation for epilepsy treatment.

A 4.5 µW Miniaturized 3-Channel Wireless Intra-Cardiac Acquisition System.

This article presents a chip designed for wireless intra-cardiac monitoring systems. The design consists of a three-channel analog front-end, a pulse-width modulator featuring output-frequency offset and temperature calibration, and inductive data telemetry. By employing a resistance boosting technique in the instrumentation amplifier feedback, the pseudo-resistor exhibits lower non-linearity, leading to a total harmonic distortion of below 0.1%. Furthermore, the boosting technique enhances the feedback resistance, leading to a reduction in the size of the feedback capacitor and, consequently, the overall size. To make the modulator's output frequency resilient to temperature and process changes, coarse and fine-tuning algorithms are used. The front-end channel is capable of extracting the intra-cardiac signal with an effective number of bits of 8.9, while exhibiting an input-referred noise of less than 2.7 µVrms, and consuming 200 nW per channel. The front-end output is encoded by an ASK-PWM modulator, which drives an on-chip transmitter at 13.56 MHz. The proposed System-on-Chip (SoC) is fabricated in a 0.18 µm standard CMOS technology and consumes 4.5 µW while occupying 1.125 mm2.