Theory of non-integer high-harmonic generation in a topological surface state

High harmonic generation is a versatile experimental technique for probing ultrafast electron dynamics. While in the past it has been employed typically in dielectrics and semiconductors, recently high harmonic generation was also observed from a topological surface [Schmid et al., Nature 593, 385 (2021)]. It has been found that harmonic orders in the intermediate range of 13-18 continuously shift when the carrier envelope phase (CEP) is varied. In this work, we adopt a minimal model of the topological surface state and calculate analytically the high-harmonic spectrum. We derive formulae describing the parametric dependencies of CEP shifts in high harmonics; in particular, we have a transparent result for the shift of the (peak) frequency ω when changing the CEP φ: dω/dφ=−2f¯′ω/ω0, where ω0 describes the fundamental driving frequency and f¯′ characterizes the chirp of the driving laser pulse. We compare the analytical formula to full-fledged numerical simulations finding only 17% average absolute deviation in dω/dφ. Our analytical result is fully consistent with experimental observations. It therefore provides the first understanding of the phenomenon of CEP shifts in solids based on analytically derived parametric dependencies

Semiconductor Bloch-equations formalism: Derivation and application to high-harmonic generation from Dirac fermions

We rederive the semiconductor Bloch equations emphasizing the close link to the Berry connection. Our rigorous derivation reveals the existence of two further contributions to the current, in addition to the frequently considered intraband and polarization-related interband terms. The extra contributions become sizable in situations with strong dephasing or when the dipole-matrix elements are strongly wave-number dependent. We apply the formalism to high-harmonic generation for a Dirac metal. The extra terms add to the frequency-dependent emission intensity (high-harmonic spectrum) significantly at certain frequencies changing the total signal up to a factor of 10

Cancer immunotherapy is accompanied by distinct metabolic patterns in primary and secondary lymphoid organs observed by non-invasive in vivo18F-FDG-PET

Purpose: Cancer immunotherapy depends on a systemic immune response, but the basic underlying mechanisms are still largely unknown. Despite the very successful and widespread use of checkpoint inhibitors in the clinic, the majority of cancer patients do not benefit from this type of treatment. In this translational study, we investigated whether noninvasive in vivo positron emission tomography (PET) imaging using 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) is capable of detecting immunotherapy-associated metabolic changes in the primary and secondary lymphoid organs and whether this detection enables the prediction of a successful anti-cancer immune response. Methods: RIP1-Tag2 mice with progressed endogenous insular cell carcinomas underwent a combined cancer immunotherapy consisting of CD4+ T cells plus monoclonal antibodies (mAbs) against programmed death ligand-1 (PD-L1) and lymphocyte activation gene-3 (LAG-3) or a sham treatment after radiation-mediated immune cell depletion. A second cohort of RIP1-Tag2 mice underwent exclusive checkpoint inhibitor therapy (CIT) using anti-PD-L1/LAG-3 mAbs or sham treatment without initial immune cell depletion to mimic the clinical situation. All mice were monitored by 18F-FDG-PET combined with anatomical magnetic resonance imaging (MRI). In addition, we retrospectively analyzed PET / computed tomography (CT) scans (PET/CT) regarding 18F-FDG uptake of CIT-treated metastatic melanoma patients in the spleen (n=23) and bone marrow (BM; n=20) as well as blood parameters (n=17-21). Results: RIP1-Tag2 mice with advanced insular cell carcinomas treated with combination immunotherapy exhibited significantly increased 18F-FDG uptake in the spleen compared to sham-treated mice. Histopathology of the spleens from treated mice revealed atrophy of the white pulp with fewer germinal centers and an expanded red pulp with hyperplasia of neutrophils than those of sham-treated mice. Immunohistochemistry and flow cytometry analyses of the spleens revealed a lower number of T cells and a higher number of neutrophils compared to those in the spleens of sham-treated mice. Flow cytometry of the BM showed enhanced activation of T cells following the treatment schemes that included checkpoint inhibitors. The ratio of 18F-FDG uptake at baseline to the uptake at follow-up in the spleens of exclusively CIT-treated RIP1-Tag2 mice was significantly enhanced, but the ratio was not enhanced in the spleens of the sham-treated littermates. Flow cytometry analysis confirmed a reduced number of T cells in the spleens of exclusively CIT-treated mice compared to that of sham-treated mice. A retrospective analysis of clinical 18F-FDG-PET/CT scans revealed enhanced 18F-FDG uptake in the spleens of some successfully CIT-treated patients with metastatic melanoma, but there were no significant differences between responders and non-responders. The analysis of the BM in clinical 18F-FDG-PET/CT scans with a computational segmentation tool revealed significantly higher baseline 18F-FDG uptake in patients who responded to CIT than in non-responders, and this relationship was independent of bone metastasis, even in the baseline scan. Conclusions: Thus, we are presenting the first translational study of solid tumors focusing on the metabolic patterns of primary and secondary lymphoid organs induced by the systemic immune response after CIT. We demonstrate that the widely available 18F-FDG-PET modality is an applicable translational tool that has high potential to stratify patients at an early time point

Non-invasive estimation of split renal function from routine 68Ga-SSR-PET/CT scans

ObjectivePatients with impaired kidney function are at elevated risk for nephrotoxicity and hematotoxicity from peptide receptor radionuclide therapy (PPRT) for advanced neuroendocrine tumors. Somatostatin receptor (SSR)-PET/CT imaging is the method of choice to identify sufficient SSR expression as a prerequisite for PRRT. Therefore, our study aimed to explore whether split renal function could be evaluated using imaging data from routine SSR-PET/CT prior to PRRT.MethodsIn total, 25 consecutive patients who underwent SSR-PET/CT (Siemens Biograph mCT®) before PRRT between June 2019 and December 2020 were enrolled in this retrospective study. PET acquisition in the caudocranial direction started at 20 ± 0.5 min after an i.v. injection of 173 ± 20 MBq [68Ga]Ga-ha DOTATATE, and the kidneys were scanned at 32 ± 0.5 min p.i. The renal parenchyma was segmented semi-automatically using an SUV-based isocontour (SUV between 5 and 15). Multiple parameters including SUVmean of renal parenchyma and blood pool, as well as parenchyma volume, were extracted, and accumulation index (ACI: renal parenchyma volume/SUVmean) and total kidney accumulation (TKA: SUVmean x renal parenchyma volume) were calculated. All data were correlated with the reference standard tubular extraction rate (TER-MAG) from [99mTc]Tc-MAG3 scintigraphy and glomerular filtration rate (GFRCDK − EPI).ResultsSUVmean of the parenchymal tracer retention showed a negative correlation with TERMAG (r: −0.519, p < 0.001) and GFRCDK − EPI (r: −0.555, p < 0.001) at 32 min p.i. The herein-introduced ACI revealed a significant correlation (p < 0.05) with the total tubular function (r: 0.482), glomerular renal function (r: 0.461), split renal function (r: 0.916), and absolute single-sided renal function (r: 0.549). The mean difference between the split renal function determined by renal scintigraphy and ACI was 1.8 ± 4.2 % points.ConclusionThis pilot study indicates that static [68Ga]Ga-ha DOTATATE PET-scans at 32 min p.i. may be used to estimate both split renal function and absolute renal function using the herein proposed “Accumulation Index” (ACI)

Computed diffusion weighted imaging (cDWI) and voxelwise-computed diffusion weighted imaging (vcDWI) for oncologic liver imaging: A pilot study

Objective: Aim of the study was to evaluate the influence of the selection of measured b-values on the precision of cDWI in the upper abdomen as well as on the lesion contrast of PET-positive liver metastases in cDWI and vcDWI. Methods: We performed a retrospective analysis of 10 patients (4 m, 63.5 ± 12.9 y/o) with PET-positive liver metastases examined in 3 T-PET/MRI with b = 100,600,800,1000 and 1500s/mm2. cDWI (cb1000/cb1500) and vcDWI were computed based on following combinations: i) b = 100/600 s/mm2, ii) b = 100/800 s/mm2, iii) b = 100/1000s/mm2, iv) b = 100/600/1000s/mm2 v) all measured b-values. Mean signal intensity (SI) and standard deviation (SD) in the liver, spleen, kidney, bone marrow and in liver lesions were acquired. The coefficient of variation (CV = SD/SI), the differences of SI between measured and calculated high b-value images and the lesion contrast (SI lesion/liver) were computed. Results: With increasing upper measured b-values, the CV in cDWI and vcDWI decreased (CV in the liver in cb1500: 0.42 with b100/600 s/mm2 and 0.28 with b100/b1000s/mm2) while the differences of measured and calculated b-value images decreased (in the liver in cb1500: 30.7% with b = 100/600 s/mm2, 19.7% with b100/b1000s/mm2). In diffusion-restricted lesions, lesion contrast was at least 1.6 in cb1000 and 1.4 in cb1500, respectively, with an upper measured b-value of b = 800 s/mm2 and 2.1 for vcDWI with an upper measured b-value of b = 1000s/mm2. Overall, the lesion contrast was superior in cb1500 and vcDWI compared to cb1000 (15% and 11%, respectively). Conclusion: Measuring higher upper b-values seems to lead to more precise computed high b-value images and a decrease of CV. vcDWI provides a comparable lesion contrast to b = 1500s/mm2 and offers additionally the reduction of T2 shine-through effects. For vcDWI, measuring b = 1000s/mm2 as upper b-value seems to be necessary to guarantee good lesion visibility in the liver based on our preliminary results