Abstract When hearing fails, cochlear implants (CIs) restore auditory perception. Yet, coding of spectral information remains a bottleneck because each electrode broadly activates the auditory nerve. As light can be more conveniently confined, optical (o)CIs present an alternative. Here, we combined expression of the potent channelrhodopsin ChReef in spiral ganglion neurons (SGNs) with oCIs comprising 5–10 green LEDs in gerbils. This combination enabled systematic comparison of encoding intensity and spectral information by individual oCI channels to acoustic and electrical stimulation within a translationally feasible energy range. Recordings from the inferior colliculus (ICC) showed that ChReef aligned SGN light sensitivity with LED radiant fluxes: ICC activity had thresholds <200 nJ and reached a maximum equivalent to that achieved with 51 dB SPL pure tones. Multichannel oCIs enabled tonotopically ordered, spectrally distinct stimulation that more closely resembled acoustic stimulation than did electrical stimulation. Some LEDs elicited multiple spectral peaks at higher intensities. Linear discriminant analysis of ICC activity indicated improved channel discriminability for optical over electrical stimulation. In summary, µJ-oCI-stimulation achieves improved spectral resolution over state-of-the-art electrical stimulation. The Paper Explained Problem Electrical cochlear implants (eCIs) partially restore speech comprehension in most of >1 million otherwise deaf users, who still face challenges hearing in daily situations. This is primarily due to poor spectral selectivity of electrical sound encoding. Spatially more confined optogenetic activation of the auditory nerve by optical cochlear implants (oCI) promises to overcome this limitation. However, a thorough characterization of bionic coding of sound information by multichannel oCI in a clinically translatable energy range is needed to evaluate the potential for improved hearing restoration. Results Here, we combine the potent channelrhodopsin ChReef and 10-channel oCI based on green LEDs in gerbils and characterize their utility for encoding of spectral and intensity information by individual channels using multielectrode array recordings from the midbrain. ChReef enabled activation of the auditory pathway with nJ thresholds and midbrain activity equivalent to that achieved with 51 dB SPL pure tones with low µJ radiant energy. The cochlear spread of excitation and channel discriminability in ICC activity substantially narrowed the gap to acoustic stimulation compared to state-of-the-art electrical stimulation. Impact Our work demonstrates great potential of multichannel optogenetic stimulation for encoding sound frequency information within a translationally feasible energy range.

Optogenetic control is used to manipulate the activity of specific cell types in vivo for a variety of biological and clinical applications. Here we report ChReef, an improved variant of the channelrhodopsin ChRmine. ChReef offers minimal photocurrent desensitization, a unitary conductance of 80 fS and closing kinetics of 30 ms, which together enable reliable optogenetic control of cells at low light levels with good temporal fidelity and sustained stimulation. We demonstrate efficient and reliable red-light pacing and depolarization block of ChReef-expressing cardiomyocyte clusters. We used adeno-associated-virus-based gene transfer to express ChReef in retinal ganglion cells, where it restores visual function in blind mice with light sources as weak as an iPad screen. Toward optogenetic hearing restoration, ChReef enables stimulation of the auditory pathway in rodents and non-human primates with nanojoule thresholds, enabling efficient and frequency-specific stimulation by LED-based optical cochlear implants. ChReef is an optogenetic actuator for sustained optogenetic control of excitable cells in a variety of preclinical applications.

Optogenetics enables insights into the development of neural diseases. Custom-designed neural probes are necessary to access targeted brain regions. Multifunctional and mechanically flexible probes with minimal footprint, comprising fluidic channels for drug delivery, light sources for optical stimulation, and micro electrodes for electro-physiological readout are beneficial due to reduced tissue trauma and consequently increased long-term stability. This study introduces a mechanically compliant neural probe that provides microfluidic channels and electrodes arranged close to fluidic outlet ports. The key challenge is to open the fluidic inlet and outlet ports avoiding potential channel clogging. A novel laserbased patterning process is demonstrated using a 248 nm KrF excimer laser. It offers high design flexibility in positioning the fluidic ports along the fluidic channels, as well their contamination-free opening under dry conditions. The laser patterning process applies reflective metal layers inside the fluidic channels, confining the laser ablation to the channel cover, thus minimizing potential damage of the channel substrate. Based on its high reflectivity and correspondingly low absorption and transmission at the applied laser wavelength, aluminium is determined to be the best choice for this protective layer.

Compared to conventional rigid silicon probes, flexible penetrating neural implants exhibit improved mechanical compliance with brain tissue, enabling high-quality neural recordings over extended periods of time. However, the length of the implantable shank and extension cable of most flexible devices falls short of clinical electrodes used in diagnostics and treatment of neurological disorders. In this study, we demonstrate the design, fabrication, and in vivo validation of polyimide-based neural probes with a thin spiral-shaped cable that reaches a length of 27 centimeters, comparable to that of clinical electrodes. The spiral probe comprises a 3.9-mm-long, 75-280-mu mwide and 10-mu m-thick implantable shank with 24 linearly placed gold microelectrodes (diameter: 20 mu m; electrode pitch: 150 mu m) placed either close to the shank edge or centered on the shank. The electrical impedance of the microelectrodes was-266 k ohm at 1 kHz measured in vitro. In acute rodent experiments, we recorded highquality local field potentials (e.g., cortical slow waves and hippocampal gamma activity), single and multiunit activities. In addition, the probes could simultaneously detect the activity of about 10 well-isolated single units, with an average spike amplitude of 65 mu V. Furthermore, devices chronically implanted in rats successfully recorded spiking activity over several consecutive days. As demonstrated here, the developed spiral probes can be applied to various tasks, such as the laminar analysis of brain oscillations or the study of the sleep-wake cycle in naturally sleeping animals. In conclusion, our flexible probe design may stimulate the development of novel implantable devices for application in large animal models or clinical settings.

Abstract This paper reports on new schemes based on the concept of tri‐state switching for routing linear arrays of light‐emitting diodes (LEDs) on slim substrates. The schemes use a minimal number of wires in single‐metal planar technologies, where wires are not allowed to cross. They have in common that the number of LEDs, NL, addressable by NW wires is given by NL = 4NW − 6. The designs are built on a family of hierarchically interconnected structures with (2n+1 − 2) LEDs and (2n−1 + 1) wires, for positive integers n. A process termed linear expansion straightforwardly extends them to arbitrary values of NW and adds 4 LEDs with each additional wire. Expressions for series resistances and the average wire length normalized to the array length are derived. In hierarchical designs, the average normalized wire length asymptotically approaches 7/12 for large n. A matrix formulation graphically elucidates the new interconnection schemes.

This study reports on a fully autonomous system comprising a wireless headstage and an array of micro light-emitting diodes (µLED) integrated in a flexible neural probe for optogenetic experiments. The 49 µLEDs (50×50 µm 2 ) are arranged at a minimal pitch of only 100 µm. The µLED-based neural probes are realized using a novel, single-sided fabrication process on the expitaxial sapphire substrate that avoids the delicate µLED transfer using wafer bonding and laser lift-off. The absolute optical power per µLED is 1.1 mW at 465 nm peak wavelength, resulting in an emittance of more than 500 mW/mm 2 at the µLED surface. The µLEDs of the optical neural probes are powered and controlled by a compact (diameter 18.7 mm, height 19.8 mm), light-weight (6.44 g), modular headstage. It enables the simultaneous operation of multiple probes serially addressing up to two arrays with each up to 16×16 µLEDs for about 2 h under continuous operation.

This paper reports on the development, characterization and in vivo validation of compact optical neural probes. These novel intracerebral devices comprise micro light-emitting diodes (μLEDs) integrated along their slender probe shanks with up to 20 μLEDs per device. Blue light with a peak wavelength of 455 nm is emitted from circular apertures 100 μm in diameter. The μLEDs are structured on GaN-on-sapphire wafers and subsequently transferred onto silicon (Si) carrier wafers. The wafer-scale transfer process provides the opportunity to process the functional GaN layer stack from both sides and hence enables maximizing the efficiency of the μLEDs. Combined with standard MEMS fabrication processes for Si, linear μLED arrays with small inter-μLED distances are achieved on thin probe shanks with cross-sections measuring 150 μm × 65 μm. Devices are interconnected using highly flexible polyimide cables in order to mechanically decouple them from the peripheral electronics during in vivo experiments. Assembled probes emit a peak optical radiant flux of 440 μW (emittance 56 mW mm-2) at 5 mA driving current. Thermal characterization of test probes reveals a temperature increase of 1.5K measured using an integrated thermistor. Electrical functionality stress tests have been carried out to evaluate the device passivation against the physiological environment. It is estimated to endure at least 48 h during continuously pulsed μLED operation. A compact driving circuitry enables low-noise μLED operation in in vivo optogenetic experiments. The radiant flux necessary to elicit an acceptable neuronal response is determined between 1.36 μW and 17.5μW. Probe validation successfully demonstrates the layer-specific stimulation in the cortex in multiple in vivo trials.

To evaluate feasibility in terms of cost for special treatment procedures across different modalities. An analysis of the cost of alternative state of the art treatment modalities was done to evaluate the necessity of more treatment options, compared to the financial gain provided by each. We used the 2019 Hospital Outpatient Prospective Payment System (HOPPS) to determine reimbursement for each treatment and assumptions on the time of physicist involvement, treatment planning, treatment time, time of radiation oncologist involvement (e.g. for gammaknife where the radiation oncologist stay during treatment), number of fractions per patient, average salaries and initial cost of modality and continuing cost of service contracts. We assumed one source exchange for gammaknife to extend its useful live. We did not include any existing overhead that will be the same between these modalities, rather just the cost of what is needed additionally for some modalities. We determined the maximum number of fractions that can be treated annually for each modality and the expected lifetime of each modality. We then calculated the number of patients needed annually to cover cost. For stereotactic radiosurgery modalities, i.e. CyberKnife, Linac-based, Linac/MRI, and gammaknife, the annual breakeven points were 25, 34, 41, and 74 patients respectively. For HDR the breakeven was 31 patients each year and 10 for a hyperthermia unit. For protons the number is higher with 152 patients. For each modality there is a limit on the number of patients that can be treated annually, depending on treatment time and common fractionations used for each modality. This favored Linac-based SRS and SBRT where the annual capacity was 1020 patients, because it was assumed that they are dedicated to stereotactic treatments, i.e. few fractions per patient and fastest treatment time. The annual capacity of patients treated with protons were 254, because of the assumption of 25 fractions per patient on average. For Gammaknife, CyberKnife, Linac/MRI, hyperthermia, and HDR the limits were 524, 331, 337, 104, and 433 respectively, because of long treatment times and/or planning times. Although hyperthermia needed the lowest number of patients to breakeven, its gain and limit on patient's treated annually were the lowest because of a large need of physics and therapy time and relatively high service contracts. For large centers where there might be a larger number of patients that might benefit from a given modality, the cost can be reduced as staff gain more expertise to do these cases faster. Accountability for resources must be balanced by the number of patients that might benefit from it. Having more options of different modalities for state-of-the-art patient care might increase the potential number of patients and a center's research potential, but it will also decrease the gain of each modality because of staff's time, expertise, and service cost.

Electrical cochlear implants (eCIs) partially restore hearing and enable speech comprehension to more than half a million users, thereby re-connecting deaf patients to the auditory scene surrounding them. Yet, eCIs suffer from limited spectral selectivity, resulting from current spread around each electrode contact and causing poor speech recognition in the presence of background noise. Optogenetic stimulation of the auditory nerve might overcome this limitation as light can be conveniently confined in space. Here, we combined virus-mediated optogenetic manipulation of cochlear spiral ganglion neurons (SGNs) and microsystems engineering to establish acute multi-channel optical cochlear implant (oCI) stimulation in adult Mongolian gerbils. oCIs based on 16 microscale thin-film light-emitting diodes (mu LEDs) evoked tonotopic activation of the auditory pathway with high spectral selectivity and modest power requirements in hearing and deaf gerbils. These results prove the feasibility of mu LED-based oCIs for spectrally selective activation of the auditory nerve.

This paper reports on the fabrication, assembly, characterization and validation of a novel opto-electrical cardiac stimulator designed to augment a mechanical pacing device. The integration of miniaturized electrodes and blue light-emitting diode (LED) chips on the pacer tip with a diameter of 1 mm enables the application of multimodal stimuli in one location on the surface of isolated murine hearts. The opto-electrical stimulator is based on two separate polyimide (PI) substrates each with a thickness of 10 μm combined into a functional unit based on dedicated assembly and encapsulation processes using silicone rubber. The experimental validation in isolated, whole hearts compares electrical, optical and mechanical stimuli exerted at frequencies of up to 8 Hz on Langen-dorff-perfused hearts expressing channelrhodopsin-2. The integrated iridium oxide electrodes implemented above the LED chips enable simultaneous electrical recordings of local cardiac electrical activity.

Rotation setup errors for SRS treatments are typically less than two degrees which usually causes less dosimetry discrepancy for a typical SRS treatment as the target size is likely less than 4 cm. However this might not be true for the single isocenter and multiple metastatic targets' technique where, the distances between the isocenter of the treatment and those tumor centers can be very large. A 6DOF couch can be used to correct this setup error by using optical surface and/or Conebeam CT (CBCT) images. The accuracy and consistence between optical surface and CBCT images were studied. The CBCT system and optical surface images of an SRS phantom were taken at different pitch, roll, and rotation angles varied from -3 to 3 degrees by intentionally changing values on the service console. A total 39 combinations of pitch, roll, and rotations using the 6DOF couch were generated. The optical surface images were taken and Vision RT software was used to determine the rotation angles and isocenter shifts. Eight CBCT images corresponding to +- 3 degree changes in pitch, roll, and rotation were taken. The center positions of the 5 tungsten carbide BBs contained in the SRS QA phantom were determined using in-house software. A least square fit was used to determine translation/rotation parameters. Among the 39 calculations from optical images, the maximum rotation angle differences were 0.2, 0.1, and -0.2 degrees for pitch, roll, and couch rotation, respectively. The maximum isocenter shifts were -0.80 mm, 0.70 mm, and -0.10 mm in lateral, longitudinal, and vertical axes, respectively. The maximum residual rotation angles from analysis of CBCT images were 0.20 degree for pitch, roll, and rotation. By using 6DOF couch, the rotation errors can be reduced dramatically compared to initial rotation errors. To overcome this rotation errors without 6DOF couch, one has to introduce extra margin for target which is far away from the treatment iso-center. Six DOF can avoid extra CTV-PTV margin. The residual rotational errors studied for the couch were less than 0.2 degree. This accuracy for the 6DOF system is sufficient for SRS applications even for single isocenter multiple tumor technique and extra CTV-PTV margin might be not necessary for some cases.

This paper reports on the fabrication and characterization of spherical micro-lenses ( μ-lenses) made from polydimethylsiloxane (PDMS) and their integration into optogenetic implants based on micro light-emitting diodes ( μLEDs). The μ-lenses are fabricated using a reusable silicon mold realized by wet chemical HNA (hydrofluoric, nitric and acetic acid) etching. It applies a masking layer with openings as small as 5 μm and was optimized for hemispherical μ-lens cavities of low surface roughness ( ). The μ-lenses with diameters down to 10 μm are realized by PDMS molding using a polymeric release layer (PRL) improving the μ-lens release and enabling Ra values below 5 nm. Linear μ-lens arrays are transferred onto the emission side of μLEDs comprising integrated conical concentrators (CCs). The PDMS-filled CCs improve the μ-lens emission behavior by light reflection at the interface between the polymeric probe substrate and PDMS, without increasing the overall probe dimensions. Using μLEDs with integrated μ-lens arrays in combination with CCs, the overall light extraction of the optical implants is increased by 115% and 83% in air and water, with the peak intensity raised by 145% and 95%, respectively.

This paper reports on the development of a low-temperature plasma annealing process for indium tin oxide (ITO) thin-films deposited by magnetron sputtering. The study investigates the influence of the type of plasma (argon (Ar) vs. oxygen (O-2)) and its duration on the optical transmission coefficient and electrical resistivity of the films depending on the power and O-2 concentration during their deposition. A low sputtering power of 100 W combined with an O-2 concentration of 6 vol% followed by a 40-min Ar plasma anneal at 300 W produces ITO films with an average transmission of 94% in the visible spectrum and a resistivity of 2.3 x 10(-3) Omega cm. Sputtering without O-2 results in a transmission of 89% and a resistivity of 9 x 10(-4) Omega cm. The annealing depth is found to be 370 nm. We deposited and annealed conductive, transparent ITO tracks below 50 degrees C on a polyimide substrate and thereby operated integrated light sources on a fully transparent and highly flexible optical probe.

Functional imaging of tumor and normal tissue physiology provides novel opportunities to further optimize radiation therapy (RT) treatments by identifying refined critical structures and biological target volumes (BTVs) within the tumor for preferential targeting. Advances in functional imaging and adaptive RT techniques have the potential to lead to the development of improved dose–response relationships for normal tissues and RT treatments that are tailored to individual patients. In this “Oncology Scan” for the special issue on Imaging in Radiation Oncology, members of the physics editorial team discuss 3 thought-provoking articles that reflect recent and noteworthy advances in the combined use of functional imaging and adaptive RT to exploit heterogeneity in tumor and normal tissue biology. First, Welz et al ( 1 Welz S. Mönnich D. Pfannenberg C. et al. Prognostic value of dynamic hypoxia PET in head and neck cancer: Results from a planned interim analysis of a randomized phase II hypoxia-image guided dose escalation trial. Radiother Oncol. 2017; 124: 526-532 Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar ) present early results of a phase 2 clinical trial aimed at prospectively determining the prognostic value of tumor hypoxia defined by [18F]fluoromisonidazole (FMISO)–positron emission tomography (PET)/computed tomography (CT) and targeting hypoxic tumor volumes with dose escalation in patients with locally advanced squamous cell carcinomas of the head and neck (LASCCHN). Second, Lapointe et al ( 2 Lapointe A. Bahig H. Blais D. et al. Assessing lung function using contrast-enhanced dual-energy computed tomography for potential applications in radiation therapy. Med Phys. 2017; 44: 5260-5269 Crossref PubMed Scopus (18) Google Scholar ) present a novel method for obtaining functional information about normal lung tissue using dual-energy CT (DECT). Third, Lee et al ( 3 Lee E. Zeng J. Miyaoka R.S. et al. Functional lung avoidance and response-adaptive escalation (FLARE) RT: Multimodality plan dosimetry of a precision radiation oncology strategy. Med Phys. 2017; 44: 3418-3429 Crossref PubMed Scopus (35) Google Scholar ) present preliminary results of a study combining functional lung avoidance and dose escalation to BTVs for non–small cell lung cancer (NSCLC) patients. Treatment planning objectives are expanded to include reduction in dose to 99mTc-labeled macro aggregated albumin ([99mTc]MAA)–single photon emission computed tomography (SPECT)/CT perfused lung and redistribution of an escalated boost dose within a [18F]fluorodeoxyglucose (FDG)-PET/CT–defined volume. The innovations presented in these 3 articles consist of using established physiologic imaging techniques in a novel way to enhance treatment planning in radiation oncology.

This study reports the realization of an optical cochlear implant (oCI) with optimized thermomechanical properties for optogenetic experiments. The oCI probe comprises 144 miniaturized light-emitting diodes (μLEDs) distributed along a bendable, 1.5-cm-long, 350-μm-wide and 26-μm-thick probe shaft, individually controlled via a n × p matrix interconnection. In contrast to our earlier approach based on polyimide (PI) and epoxy resin with different thermal expansion coefficients, the μLEDs and interconnecting wires are now embedded into a triple-layer stack of a single, biocompatible, and highly transparent epoxy material. The new material combination results in a pronounced reduction of thermomechanical bending in comparison with the material pair of the earlier approach. We developed a spin-coating process enabling epoxy resin layers down to 5 μm at thickness variations of less than 7% across the entire carrier wafer. We observed that the cross-linking of epoxy resin layers strongly depends on the spin-coating parameters which were found to be correlated to a potential separation of epoxy resin components of different densities. Furthermore, various metallization layers and corresponding adhesion promoting layers were investigated. We identified the combination of silicon carbide with a titanium-based metallization to provide the highest peeling strength, achieving an adhesion to epoxy improved by a factor of two. In order to obtain a high process yield, we established a stress-free implant release using the electrochemical dissolution of a sacrificial aluminum layer. The direct comparison of oCI probe variants using a single epoxy material and the combination of PI and epoxy resin revealed that the epoxy-resin-only probe shows minimal thermomechanical probe bending with a negligible hysteresis. The thermal probe characterization demonstrated that the temperature increase is limited to 1 K at μLED DC currents of up to 10 mA depending on the stimulation duration and the medium surrounding the probe. The optical output power and peak wavelengths of the new oCI variant were extracted to be 0.82 mW and 462 nm when operating the μLEDs at 10 mA, 10 kHz, and a duty cycle of 10%. The optical power corresponds to a radiant emittance of 407 mW/mm2, sufficient for optogenetic experiments using channelrhodopsin-2.

The introduction of advanced techniques and technology in radiotherapy has greatly improved our ability to deliver highly conformal tumor doses while minimizing the dose to adjacent organs at risk. Despite these tremendous improvements, there remains a general concern about doses to normal tissues that are not the target of the radiation treatment; any "nontarget" radiation should be minimized as it offers no therapeutic benefit. As patients live longer after treatment, there is increased opportunity for late effects including second cancers and cardiac toxicity to manifest. Complicating the management of these issues, there are unique challenges with measuring, calculating, reducing, and reporting nontarget doses that many medical physicists may have limited experience with. Treatment planning systems become dramatically inaccurate outside the treatment field, necessitating a measurement or some other means of assessing the dose. However, measurements are challenging because outside the treatment field, the radiation energy spectrum, dose rate, and general shape of the dose distribution (particularly the percent depth dose) are very different and often require special consideration. Neutron dosimetry is also particularly challenging, and common errors in methodology can easily manifest as errors of several orders of magnitude. Task Group 158 was, therefore, formed to provide guidance for physicists in terms of assessing and managing nontarget doses. In particular, the report: (a) highlights major concerns with nontarget radiation; (b) provides a rough estimate of doses associated with different treatment approaches in clinical practice; (c) discusses the uses of dosimeters for measuring photon, electron, and neutron doses; (d) discusses the use of calculation techniques for dosimetric evaluations; (e) highlights techniques that may be considered for reducing nontarget doses; (f) discusses dose reporting; and (g) makes recommendations for both clinical and research practice.

The objective of this prospective study was to assess the safety and efficacy of Kypho-IORT for painful vertebral body (VB) fractures in cancer patients. Patients with symptomatic osteolytic vertebral body metastasis underwent Kypho-IORT: kyphoplasty procedures and intraoperative radiotherapy with the ZEISS INTRABEAM System followed by cement augmentation. Tumors were limited to vertebral body (sector 1) using the International Spine Radiosurgery Consortium (ISRC) anatomic classification system, SINS scores of 7-12, and Bilsky grade of 0. Intraoperative CT delineation of gross tumor volume, needle applicator tip, and OAR was done with deformable image registration, integrating pre-operative CT and MRI images. 10 Gy was prescribed to a distance from the source tip to the distal boundary, based on the mean radius plus SD. The prescription was limited by a maximum dose limit to the spinal cord of 12 Gy. Quality of Life Measurements were done using the QOL [EORTC QLQ-C30 (version 3)], the Brief Pain Inventory (BPI), Numerical Rating Pain Scale (NRPS), ambulation, and narcotic use pre- and post-procedure at 1-week, 3-month, 6-month, 9-month, 1-year, and 2-year intervals. The involved spine will be imaged at 3-month intervals up to one year and at 2 years post-procedure. 7 vertebral levels were treated. All patients were discharged home within 12 hours of the Kypho-IORT procedure. There was a statistically significant reduction in patient reported NPRS scores from preoperative baseline within 2 weeks (6.57±1.4 preoperative versus 3.57±2.57 postoperatively; p=0.0189). After 3 months, one patient with metastatic rectal cancer suffered local progression. Patients also experienced better quality of life with respect to bone metastasis-specific issues. The QLQ-C30 is able to discriminate among patients with varying responses. Kypho-IORT is a safe treatment option for potentially unstable spinal metastases. Patient reported pain scores significantly improve within two weeks with improved quality of life. Long-term follow up is necessary to further evaluate efficacy.

Purpose: The objective of this study was to assess a contemporary cohort of patients with multiple myeloma referred for palliative radiation to the mobile spine for clinical and radiological responses. Materials/Methods: The records of patients treated between 2009 and 2016 with radiotherapy for multiple myeloma of the spine were retrospectively reviewed. Demographics, systemic therapy, radiation dose, number of fractions, radiographic response based upon adapted RECIST criteria, and symptomatic response were recorded. Results: Eighty eight patients and 98 treatment courses were analyzed. All courses were analyzed for symptomatic response and 61 of the treatment courses were available for radiologic follow-up. The median follow-up was 9.7 months with a median radiation dose of 25 Gy (12.5-50 Gy) delivered in a median of 10 fractions (5-25 fractions). Fifty-four percent of patients had a high-risk lesion. Symptomatic response as measured by a decrease of ≤5 points on the pain related scale was 83% and 34% of patients had a decrease of >5 points. Of 35% of patients that had neurologic impairments prior to treatment, improvement was identified 83% of the time. Radiographic response was noted as 13% complete response, 16% partial response, 57% stable disease, and 13% disease progression. Specifically, high-risk lesions treated with radiation alone demonstrated no regression with only 10% demonstrating partial response. Conclusion: This retrospective series of patients treated with palliative intent for multiple myeloma using various dose and fractionation schemes showed favorable symptomatic relief in most patients. Radiographic response did not correlate with clinical response with fewer patients having radiologic disease regression. Longer follow-up is necessary to determine if the lack of radiologic response is associated with clinically relevant recurrent pain.

This paper reports on the yield optimization of a wafer-level indium (In)-based bonding process for joining 4-inch sapphire and silicon (Si) wafers. The process allows to realize neural probes with integrated micro light-emitting diodes (μLED) for optogenetic applications. The sapphire substrates comprise 6-μm-thick gallium nitride (GaN)-based μLEDs with lateral dimensions down to 50×50 μm 2 , which are transferred by the In-based bonding process onto gold pads on a Si wafer with interconnecting leads. Challenges that needed to be addressed in this context were the patterning of In on top of the GaN structures and thermomechanical stress limiting the overall bonding yield. The first challenge was met using a bilayer lift-off process; the yield was optimized by using an analytical model supported by an experimental study systematically varying the bond metal thickness t In and the normalized bond area A norm = A pads /A wafer , where A pads and A wafer denote the total area of all bond pads on the wafer and the wafer area, respectively. The stress-induced rupture of bond interfaces is completely suppressed when t in ≥ 3 μm and A norm ≥ 15%. The optimized In-based bonding process was successfully applied to realize 2D μLED arrays with high yield.

Significant developments over the last decades have increased the use of 3-dimensional (3D) image-guided procedures in brachytherapy, with rapid utilization of computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), and positron emission tomography (PET) imaging modalities. This has taken brachytherapy to a new level in terms of being able to control the dose to the tumor and surrounding organs. In this issue of the Oncology Scan, members of the physics editorial team present and discuss 3 interesting articles that reflect some recent and important developments within the areas of technology, imaging, and outcome analysis in image-guided brachytherapy.