Reliable Surrogates Research Articles

Can we rely on surgical clips placed during oncoplastic breast surgery to accurately delineate the tumor bedfor targeted breast radiotherapy?

Oncoplastic breast surgery (OBS) is gaining popularity among surgeons for breast-conserving surgery treatments. OBS relies on complex relocation and deformation of breast tissue involving the tumor bed (TB). In this study, we investigate the validity of using surgical clips with OBS for accurate TB delineation in adjuvant, targeted breastradiotherapy. Different OBS techniques were simulated on realistic breast phantoms. Surgical clips were used to demarcate the TB. Following tumor resection and closure, the true TB (TBTrue) was extracted. Each phantom was CT imaged at several phases of surgery in order to record pre- and post-OBS closure surgical clip displacements. Two senior radiation oncologists (ROs) were asked to delineate TBs on CTs by relying on surgical clips placedas per standard protocol, and by referring to operative notes. Their original contours, as well as those expanded using 5-15 mm margins, were compared with the accurate TBTrue using the dice similarity coefficient (DSC), Hausdorff Distance (HD), and over- and under-contoured volumes. Inter- and intra-RO contour agreements were also evaluated. Post-OBS surgical clips were significantly displaced outside the original breast quadrant. Inter- and Intra-RO TB contours were consistent, yet systematically differed from TBTrue (DSC values range = 0.38 to 0.69, and maximum HD range = 17.8 mm to 38.0mm). Using expansion margins did not improve contour congruence and caused significant over-contoured volumes. Following OBS, surgical clips alone are not reliable radiographic surrogates of TB locations and accurate TB delineation is challenging. For complex OBS cases, indication of any type of partial breast irradiation is very questionable.

When does growth rate influence fitness in a colonial marine invertebrate?

Growth rate affects body size, and larger body sizes are often associated with the capacity to produce more surviving offspring. However, the assumption that growth rate should positively relate to fitness is rarely tested, especially in colonial marine invertebrates where size and age can be decoupled. We measured growth, survival, and reproduction through repeated census of 97 colonies from two populations of a marine bryozoan in the field from settlement to the end of their reproductive season in the northern Gulf of Mexico. Despite large population differences in fitness when grown in a common garden setting, selection within populations on variation in relative growth rate prior to reproduction was similar. In both populations, colonies that grew faster early after settlement, hence were larger, did not consistently have higher fitness than colonies that grew slower after settlement. Instead, early juvenile growth was uncorrelated to later juvenile growth, and colonies that grew faster just prior to the onset of reproduction had higher fitness than colonies that grew slower during this time. Growth rates then declined with the onset of reproduction. Our results show that, rather than being a simple consequence of selection on body size, growth rate can directly affect variation in fitness in ways that are not directly attributable to juvenile size. Colony size and growth rate in modular animals are not always reliable surrogates for direct estimates of survival and reproduction, without identifying when and how growth affects fitness.

Low‐cost multi‐criteria design optimization of compact microwave passives using constrained surrogates and dimensionality reduction

AbstractDesign of contemporary microwave circuits is a challenging task. Typically, it has to take into account several performance requirements and constraints. The design objectives are often conflicting and their simultaneous improvement may not be possible; instead, compromise solutions are to be sought. Representative examples are miniaturized microwave passives where reduction of the circuit size has a detrimental effect on its electrical characteristics. Acquiring information about the best possible design trade‐offs is invaluable for the designer, yet it entails computationally expensive multi‐objective optimization (MO). MO is typically conducted using population‐based metaheuristic algorithms, the cost of which might be extremely high. If the circuit performance is evaluated using full‐wave electromagnetic (EM) analysis, this cost is often prohibitive. A workaround is the employment of fast surrogate models, and a number of surrogate‐assisted frameworks have been proposed in the literature. Unfortunately, a construction of reliable surrogates is hindered in higher dimensional parameter spaces. The recently proposed constrained modeling mitigates this issue to a certain extent by restricting the modeling process to the region containing the Pareto front to be found. This work proposes a novel surrogate‐based MO technique that involves constrained modeling and explicit reduction of the surrogate domain dimensionality. The latter is achieved through the spectral analysis of the extreme Pareto‐optimal design set obtained by local search routines. Our methodology is validated using a 15‐parameter impedance‐matching transformer with the Pareto set identified at the cost of a few hundred EM analyses of the circuit. The numerical experiments also demonstrate a significant reduction of the optimization cost as compared to the state‐of‐the‐art surrogate‐assisted MO methods.

The Block Relevance (BR) Analysis Makes the Choice of Methods for Measuring Lipophilicity and Permeability Safer and Speeds Up Drug Candidate Prioritization.

The Block Relevance (BR) analysis with its recent implementation in MATLAB is a computational tool that allows deconvoluting the balance of intermolecular interactions governing a given drug discoveryrelated phenomenon described by a QSPR/PLS model. Here we discuss a few applications to show how BR analysis can make faster and more efficient the assessment of the drug-likeness of drug candidates. First, we describe how identifying the best chromatographic system provides reliable log Poct surrogates and log P in apolar environments. Then we focus on permeability and show how BR analysis allows to check the universality of passive permeability among cell types and the identification of the PAMPA method that provides the same picture in terms of balance of intermolecular interactions as cell-based systems.

Nested Kriging with Variable Domain Thickness for Rapid Surrogate Modeling and Design Optimization of Antennas

Design of modern antennas faces numerous difficulties, partially rooted in stringent specifications imposed on both electrical and field characteristics, demands concerning various functionalities (circular polarization, pattern diversity, band-notch operation), but also constraints imposed upon the physical size of the radiators. Conducting the design process at the level of full-wave electromagnetic (EM) simulations, otherwise dictated by reliability, entails considerable computational expenses, which is another and a serious challenge. It is especially pronounced for the procedures involving repetitive EM analyses, e.g., parametric optimization. Utilization of fast surrogate models as a way of mitigating this issue has been fostered in the recent literature. Unfortunately, construction of reliable surrogates for antenna structures is hindered by their highly nonlinear responses and even more by the utility requirements: design-ready models are to be valid over wide ranges of operating conditions and geometry parameters. Recently proposed performance-driven modeling, especially the nested kriging framework, addresses these difficulties by confining the surrogate model domain to a region that encapsulates the designs being optimum with respect to the relevant figures of interest. The result is a dramatic reduction of the number of training samples needed to render a usable model. This paper introduces a variable-thickness domain, which is an important advancement over the basic nested kriging. The major benefit demonstrated using two antenna examples is a further and significant (up to seventy percent) reduction of the training data acquisition cost. It is achieved while ensuring that the model domain covers the regions containing optimum designs for various sets of performance specifications.

A systematic review of meta-analyses assessing the validity of tumour response endpoints as surrogates for progression-free or overall survival in cancer

BackgroundTumour response endpoints, such as overall response rate (ORR) and complete response (CR), are increasingly used in cancer trials. However, the validity of response-based surrogates is unclear. This systematic review summarises meta-analyses assessing the association between response-based outcomes and overall survival (OS), progression-free survival (PFS) or time-to-progression (TTP).MethodsFive databases were searched to March 2019. Meta-analyses reporting correlation or regression between response-based outcomes and OS, PFS or TTP were summarised.ResultsThe systematic review included 63 studies across 20 cancer types, most commonly non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and breast cancer. The strength of association between ORR or CR and either PFS or OS varied widely between and within studies, with no clear pattern by cancer type. The association between ORR and OS appeared weaker and more variable than that between ORR and PFS, both for associations between absolute endpoints and associations between treatment effects.ConclusionsThis systematic review suggests that response-based endpoints, such as ORR and CR, may not be reliable surrogates for PFS or OS. Where it is necessary to use tumour response to predict treatment effects on survival outcomes, it is important to fully reflect all statistical uncertainty in the surrogate relationship.

Are CIN3 risk or CIN3+ risk measures reliable surrogates for invasive cervical cancer risk?

• Discuss ASCCP guideline. • CIN3 reliable surrogates for cervical cancer? • The Pittsburgh Cervical Cancer Screening Model.

Volatile Organic Compound Based Markers for the Aroma Trait of Rice Grain

A study was conducted to determine the volatile organic compounds (VOCs) associated with rice grain aroma in 37 commonly grown lines within Uganda, as well as elites. The aim of the study was to identify potential volatile biochemical markers, if any, for the rice grain aroma trait. Certified rice seeds were obtained from the Uganda National Crops Resources Research Institute germplasm collection. The seeds were sown into experimental plots, under field conditions and the mature paddy harvested. Polished rice grains were heated to 80 oC and the liberated VOCs subjected to untargeted metabolite analysis using gas chromatography-time-of-flight mass spectrometry. In total, nine functional groups were present; hydrocarbons, alcohols, ketones, aldehydes, N-containing compounds, S-containing compounds, esters, oxygen heterocycles and carboxylic acids. More specifically, 148 VOCs were identified across the 37 rice lines, of which 48 (32.4%) including 2-acetyl-1-pyrroline (2-AP) appeared to elucidate the difference between non-aromatic and aromatic rice. Furthermore, 41 (27.7%) VOCs were found to be significantly correlated with 2-AP abundance, the principle rice aroma compound. Amongst the 41 VOCs, only ten compounds were found to contribute highly towards variation in 2-AP abundance, indicative of their possible modulation roles in regard to rice aroma. Within the ten influential volatiles, three aroma active compounds; toluene, 1-hexanol, 2-ethyl and heptane, 2,2,4,6,6-pentamethyl- were established as the most reliable biochemical surrogates to the rice aroma trait. Thus, the aforementioned compounds may be used in rice breeding programme for enhancing development of the grain aroma trait.

Application-oriented mini-plant experiments using non-conventional model foulants to evaluate new hollow fiber membrane materials

Most of literature reporting on performance of ultrafiltration membranes was performed in bench-scale experiments employing flat-sheets at operating conditions irrelevant to full-scale application. Subsequently, there is a critical need for an appropriate lab-scale testing protocol employing reliable fouling surrogates. Common individual foulants, e.g., humic acid, bovine serum albumin and sodium alginate, were extensively reported; however, their ability to resemble organic fouling by real surface waters remains questionable. In this study, potting soil extracts were investigated as reliable and inexpensive model foulants for testing the performance of new modified polyphenylene sulfone (PPSU) hollow fiber membrane modules. Assessment experiments were performed in comparison with corresponding polyethersulfone (PESU) membranes modules using mini-plant testing unit operated at full-scale conditions. At comparable total organic carbon content, aqueous extracts of four different potting soil types had different dissolved organic carbon compositions and turbidity. Humic substances were the main constituents; however, hydrophobic organic carbon (HOC) and biopolymers varied significantly. An application-oriented testing protocol comprising 24 filtration-cycles was developed. Potting soil extract feeds were emphasized to imitate chemical composition and characteristics of moderately organic-loaded surface waters, at high reproducibility, and induce typical organic fouling within experiment time. Feeds exhibiting high biopolymer content (or modest portions of biopolymer and HOC) were able to distinguish explicitly between fouling propensity of different modified membrane materials. Besides regular performance measures, fouling propensity was quantified as hydraulic irreversible fouling index (HIFI) that was related to turbidity removal; however, no consistent correlation was found with humics and low molecular weight organic fractions. Furthermore, impact of feed solution type on the interplay between membranes’ characteristics and HIFI values was investigated. Good correlation between PPSU-based membranes’ characteristics and HIFI values was noticed upon using feeds containing considerable biopolymers and HOC portions. Nevertheless, in case of PESU-based membranes, impact of improvement of pure water permeability (due to modification) was dominating.

Cost‐efficient performance‐driven modelling of multi‐band antennas by variable‐fidelity electromagnetic simulations and customized space mapping

AbstractElectromagnetic (EM) simulations have become an indispensable tool in the design of contemporary antennas. EM‐driven tasks, for example, parametric optimization, entail considerable computational efforts, which may be reduced by employing surrogate models. Yet, data‐driven modelling of antenna characteristics is largely hindered by the curse of dimensionality. This may be addressed using the recently reported domain‐confinement techniques, especially the nested‐kriging framework, which permits rendering of reliable surrogates over wide ranges of antenna parameters while greatly reducing the computational overhead of training data acquisition. Focused on modelling of multi‐band antennas, this paper attempts to reduce the cost of surrogate construction even further by incorporating variable‐fidelity simulations into the nested kriging. The principal challenge being design‐dependent frequency shifts between the models of various fidelities is handled through the development of a customized frequency scaling and output space mapping. Validation is carried out using a dual‐band dipole antenna modeled over broad ranges of operating conditions. A small training data set is sufficient to secure the predictive power comparable to that of the nested kriging model set up using solely high‐fidelity data, and by far exceeding the accuracy of conventional surrogates. Application examples for antenna optimization and experimental verification of the selected designs are also provided.

Cost-efficient surrogate modeling of high-frequency structures using nested kriging with automated adjustment of model domain lateral dimensions

Surrogate models are becoming popular tools of choice in mitigating issues related to the excessive cost of electromagnetic (EM)-driven design of high-frequency structures. Among available techniques, approximation modeling is by far the most popular due to its versatility. In particular, the surrogates are exclusively based on the sampled simulation data with no need to involve engineering insight or problem-specific knowledge. Notwithstanding, a typically high nonlinearity of system outputs and the curse of dimensionality limit the applicability of conventional methods to relatively simple structures described by a few parameters within narrow ranges thereof. A recently reported nested kriging alleviates these difficulties from the perspective of an appropriate definition of the model domain. By focusing the modeling process on the region containing design that are optimized for the selected performance figures, it enables the construction of reliable surrogates over wide ranges of geometry/material parameters and operating conditions, both at a practically acceptable computational cost. The relative model domain thickness (i.e., its lateral-to-tangential size), determines the trade-off between the surrogate region of coverage and its predictive power, the former being essential for practical applications of the model, especially design optimization. This paper proposes a simple and computationally efficient procedure for automatic selection of the thickness parameter, which, in the original version of the method, was to be selected by the user. The importance of this aspect of the modeling process and the benefits of the proposed approach are demonstrated using a dual-band dipole antenna and miniaturized microstrip coupler.

Design-oriented computationally-efficient feature-based surrogate modelling of multi-band antennas with nested kriging

Design of modern antenna structures heavily depends on electromagnetic (EM) simulation tools. EM analysis provides reliable evaluation of increasingly complex designs but tends to be CPU intensive. When multiple simulations are needed (e.g., for parameters tuning), the aggregated simulation cost may become a serious bottleneck. As one possible way of mitigating the issue, the recent literature fosters utilization of faster representations, or surrogates, of the system at hand. Notwithstanding, conventional models are severely affected by the curse of dimensionality. In practice, modelling of antenna structures described by no more than a few parameters over narrow parameter ranges is possible. In the context of the structural complexity of modern antennas, this is hardly acceptable. This paper presents a novel technique for cost-efficient design-oriented modelling of multi-band antennas. Our approach integrates a recently reported nested kriging framework and the response feature technology. This combination enables rendering of reliable surrogates valid within broad ranges of geometry parameters while using small training data sets. Benchmarking against conventional modelling methods demonstrates superiority of the proposed framework in terms of both the predictive power of the surrogate and its setup cost. Design applications for antenna optimization are discussed as well.

Recent Advances in High Frequency Modeling by Means of Domain Confinement and Nested Kriging

Development of modern high-frequency components and circuits is heavily based on full-wave electromagnetic (EM) simulation tools. Some phenomena, although important from the point of view of the system performance, e.g., EM cross-coupling effects, feed radiation in antenna arrays, substrate anisotropy, cannot be adequately accounted for using simpler means such as equivalent network representations. Consequently, the involvement of EM analysis, especially for tuning of geometry parameters, has become imperative in high-frequency electronics. Notwithstanding, excessive computational costs associated with massive full-wave simulations required by these procedures and even more by tasks such as uncertainty quantification or multi-criterial optimization, constitute a practical bottleneck. Repetitive evaluations of a structure can be facilitated by the use of fast replacement models (surrogates). Among available methods, approximation models are by far the most popular due to their flexibility and accessibility. Unfortunately, surrogate modeling of high-frequency structures is hindered by the curse of dimensionality and nonlinearity of system responses, primarily frequency characteristics. The recently proposed performance-driven techniques attempt to address this issue by appropriate confinement of the model domain to focus the modeling process only on the relevant part of the parameter space, i.e., containing the designs that are of high quality from the point of view the assumed performance figures. The nested kriging framework is perhaps the most advanced of these methods and allows for constructing reliable surrogates over broad ranges of the system parameters and operating conditions. This article summarizes the recent developments of the technique, including the basic formulation and several advancements aiming at the improvement of the surrogate predictive power or lowering the computational cost of training data acquisition. These include the incorporation of sensitivity data, as well as dimensionality reduction through principal component analysis. The problem of uniform data sampling in confined domains is also discussed. Our considerations are comprehensively illustrated using several examples of antennas and microwave circuits.

Scoring systemic lupus erythematosus (SLE) disease activity with simple, rapid outcome measures

ObjectiveExisting methods for grading lupus flares or improvement require definition-based thresholds as increments of change. Visual analogue scales (VAS) allow rapid, continuous scaling of disease severity. We analysed the performance...

3D imaging of the Parthenon sculptures: an assessment of the archaeological value of nineteenth-century plaster casts

Abstract

Implementing and Improving Pancreas SBRT: One Challenge at a Time

The role of stereotactic body radiotherapy (SBRT) is being investigated as an alternative to long-course chemoradiation in select patients with locally advanced pancreatic cancer. Implementation of this technique is complex and fraught with challenges including the proximity of dose sensitive organs, target visibility for image guidance and respiratory motion. Pancreas SBRT was introduced at our institution in 2015 and the technique has undergone multiple iterations since with the goal of improving outcomes. The aim of our current work is to establish optimal respiratory motion management for pancreas SBRT. Initially, all pancreas SBRT cases were treated with a 3 fraction regimen (21-36 Gy) using abdominal compression to minimize respiratory motion. Patients were required to have a biliary stent in situ or fiducial markers implanted prior to simulation for image guidance. Based on our initial local control and toxicity results, institutional policy changed to a 5 fraction regimen (30-50 Gy). Abdominal compression is beneficial for minimizing motion and immobilizing the patient; however, there is a concern that it also causes anatomic deformation to organs at risk (OARs) such as the stomach and duodenum, moving them closer to the target. Thus, an upfront motion assessment was introduced to determine if motion management was necessary. At the time of planning, a free breathing low dose 4D computed tomography (4DCT) scan is acquired to quantify the pancreatic motion using the fiducials. If motion amplitude is <5mm, planning proceeds without abdominal compression, potentially eliminating the problem of moving the OARs into the high dose region. If on free breathing, the motion amplitude is >5mm, either abdominal compression or Active Breathing Coordinator (ABC) is required. For patients where ABC treatment is an option, breath hold and stability assessments will follow to confirm they are suitable candidates. Performing motion assessment prior to CT simulation allows for a more personalized approach to treating patients with pancreas SBRT. Treating patients without the abdominal plate provides greater comfort for patients and has potential dosimetric benefits for OARs. As access to MRI for simulation/planning increases, the free breathing option can readily be built upon as it does not rely on any treatment accessories. Unfortunately, motion evaluation is currently limited to patients with fiducials because stents are not reliable surrogates for motion as they are quite mobile themselves. Interpreting a complex decision tree like this can be confusing for those performing the simulation, making communication and education integral to the success of the program. To date, 18 patients have undergone motion assessment. Five patients were treated free-breathing, 12 patients with abdominal compression, and 1 with ABC. The 12 patients simulated with abdominal compression had an average motion reduction of 9.2 mm to 5.2 mm, confirming the effectiveness of abdominal compression. To quantify intrafraction motion for the free-breathing option, post treatment Cone Beam Computed Tomography (CBCT) images were acquired after every fraction. Upon analysis of the CBCT data, an average overall shift of only 1.5 mm was seen, suggesting there are no issues with stability. The development of 3 different methods for treating SBRT pancreas has resulted in an approach tailored to individual patient’s motion management needs and prepared us for future technological innovations.

Species turnover in plants does not predict turnover in flower-visiting insects.

Congruence between plant and insect diversity is considered possibly useful in conservation planning, as the better known plants could be surrogates for the lesser known insects. There has been little quantification of congruence across space, especially in biodiversity rich areas. We compare here species richness, and turnover relationships between plants and flower-visiting insects across space (0.5–80 km) in natural areas of a biodiversity hotspot, the Greater Cape Floristic Region, South Africa. A total of 22,352 anthophile individuals in 198 species and 348 plant species were sampled. A comparison between the plants and anthophiles suggest significant concordance between the two assemblages. However, turnover was weaker in plants than in anthophiles. Plant turnover decreased with greater geographical distance between plot pairs. In contrast, insect turnover remained high with increasing geographical distance between plot pairs. These findings suggest that while patterns of plant diversity and distribution shape flower-visiting insect assemblages, they are not reliable surrogates. The conservation significance of these results is that specialist mutualisms are at greatest risk, and that set-asides on farms would help improve the functional connectivity leading to the maintenance of the full range of mutualisms.

Nanolipid Formulations of Benzoporphyrin Derivative: Exploring the Dependence of Nanoconstruct Photophysics and Photochemistry on Their Therapeutic Index in Ovarian Cancer Cells.

With the rapidly emerging designs and applications of light-activated, photodynamic therapy (PDT)-based nanoconstructs, photonanomedicines (PNMs), an unmet need exists to establish whether conventional methods of photochemical and photophysical characterization of photosensitizers are relevant for evaluating new PNMs in order to intelligently guide their design. As a model system, we build on the clinical formulation of benzoporphyrin derivative (BPD), Visudyne® , by developing a panel of nanolipid formulations entrapping new lipidated chemical variants of BPD with differing chemical, photochemical and photophysical properties. These are 16:0 and 20:0 lysophosphocholine-BPD (16:0/20:0 BPD-PC), DSPE-PEG-BPD and BPD-cholesterol. We show that Visudyne® was the most phototoxic formulation to OVCAR-5 cells, and the least effective was liposomal DSPE-PEG-BPD. However, these differences did not match their optical, photophysical and photochemical properties, as the static BPD quenching was highest in Visudyne, which also exhibited the lowest generation of singlet oxygen. Furthermore, we establish that OVCAR-5 cell phototoxicity also does not correlate with rates of photosensitizer photobleaching and fluorescence quantum yields in any nanolipid formulations. These findings warrant critical future studies into subcellular targets and molecular mechanisms of phototoxicity of photodynamic nanoconstructs, as more reliable prognostic surrogates for predicting efficacy to appropriately and intelligently guide their design.

Correlation between Invasive Hemodynamic Measurements and Echocardiographic Markers of LV Diastolic Function in Heart Transplant Recipients

Introduction Left ventricular diastolic dysfunction in orthotopic heart transplant patients has been thought to be a marker of rejection and predictive of increased mortality. However, standard echocardiographic measurements of diastolic function have not been validated in this population. Factors unique to transplant recipients including larger atria, younger donor hearts, and electrical dissociation between donor and recipient hearts may affect echo measurements. We evaluated the correlation between echo parameters and left-ventricular end diastolic pressure in transplant recipients. Hypothesis At one year post-transplant, standard echocardiographic markers of diastolic function do not correlate well with invasive hemodynamic measurements of diastolic function given the unique characteristics of cardiac transplantation. Methods A series of 115 consecutive heart transplant recipients at our institution between January 2010 and December 2015 who were assessed at the time of their one-year post-transplant follow-up visit with same-day echocardiograms and cardiac catheterizations were studied. Left ventricular end-diastolic pressure (LVEDP) was measured at cardiac catheterization. Echocardiographic parameters of diastolic function included E/A, septal E/e', lateral E/e', average E/e', and left atrial volume. Chart abstraction was performed for clinical data evaluation. Linear association among catheterization and echo parameters was determined by the Pearson product moment correlation coefficient. Results None of the standard echocardiographic parameters of diastolic function were well correlated with LVEDP ( Table 1 ). Only E/A had a statistically significant correlation with LVEDP, with a correlation coefficient of 0.27 (p = 0.007). Septal, lateral, and average E/e’ were predictors of death and re-hospitalization for rejection (p ≤ 0.001 for all). Conclusions Standard echocardiographic markers of diastolic function were not well-correlated with LVEDP, suggesting they are not reliable surrogates of LVEDP. However, elevated E/e’ ratio was associated with subsequent death and hospitalization for allograft rejection, implying that early mitral filling and tissue velocity may describe important allograft functional properties independent of resting LVEDP.

Different maximum latewood density and blue intensity measurements techniques reveal similar results

Annually resolved and absolutely dated Maximum Latewood Density (MXD) and Blue Intensity (BI) measurements are frequently used for reconstructing summer temperature variability over the last centuries to millennia. A direct comparison of the outcome of both methods using similar material is needed due to how quickly this method is being adopted. The application of slightly different measuring systems (hardware) and analysis tools (software) in tandem with different wood samples and preparation procedures further challenges any straightforward assessment. Here we process 26 Norway spruce samples from the upper timberline in the Polish Tatra Mountains with the six most frequently used MXD and BI applications. Although offset is found in the raw MXD and BI data (0.04–0.13 g/cm3 and 0.45–1.58 dimensionless blue intensity), interannual and longer-term fluctuations are significantly (p < 0.01) positively correlated between all MXD and BI time-series. Our results emphasize the potential of faster and cheaper, as well as overall more user-friendly techniques to generate reliable MXD surrogates for high-frequency dendroclimatological studies. Although the correlations between MXD and BI were lower than within MXD and BI, the results of growth-climate response performed for both proxies show only marginal differences. The obtained level-offset further questions the suitability of joining different density surrogates for developing long-term composite chronologies to reconstruct low-frequency climate variability.