Accuracy of an Artificial Intelligence System for Interval Breast Cancer Detection at Screening Mammography.

Background Artificial intelligence (AI) systems can be used to identify interval breast cancers, although the localizations are not always accurate. Purpose To evaluate AI localizations of interval cancers (ICs) on screening mammograms by IC category and histopathologic characteristics. Materials and Methods A screening mammography data set (median patient age, 57 years [IQR, 52-64 years]) that had been assessed by two human readers from January 2011 to December 2018 was retrospectively analyzed using a commercial AI system. The AI outputs were lesion locations (heatmaps) and the highest per-lesion risk score (range, 0-100) assigned to each case. AI heatmaps were considered false positive (FP) if they occurred on normal screening mammograms or on IC screening mammograms (ie, in patients subsequently diagnosed with IC) but outside the cancer boundary. A panel of consultant radiology experts classified ICs as normal or benign (true negative [TN]), uncertain (minimal signs of malignancy [MS]), or suspicious (false negative [FN]). Several specificity and sensitivity thresholds were applied. Mann-Whitney U tests, Kruskal-Wallis tests, and χ2 tests were used to compare groups. Results A total of 2052 screening mammograms (514 ICs and 1548 normal mammograms) were included. The median AI risk score was 50 (IQR, 32-82) for TN ICs, 76 (IQR, 41-90) for ICs with MS, and 89 (IQR, 81-95) for FN ICs (P = .005). Higher median AI scores were observed for invasive tumors (62 [IQR, 39-88]) than for noninvasive tumors (33 [IQR, 20-55]; P < .01) and for high-grade (grade 2-3) tumors (62 [IQR, 40-87]) than for low-grade (grade 0-1) tumors (45 [IQR, 26-81]; P = .02). At the 96% specificity threshold, the AI algorithm flagged 121 of 514 (23.5%) ICs and correctly localized the IC in 93 of 121 (76.9%) cases, with 48 FP heatmaps on the mammograms for ICs (rate, 0.093 per case) and 74 FP heatmaps on normal mammograms (rate, 0.048 per case). The AI algorithm correctly localized a lower proportion of TN ICs (54 of 427; 12.6%) than ICs with MS (35 of 76; 46%) and FN ICs (four of eight; 50% [95% CI: 13, 88]; P < .001). The AI algorithm localized a higher proportion of node-positive than node-negative cancers (P = .03). However, no evidence of a difference by cancer type (P = .09), grade (P = .27), or hormone receptor status (P = .12) was found. At 89.8% specificity and 79% sensitivity thresholds, AI detection increased to 181 (35.2%) and 256 (49.8%) of the 514 ICs, respectively, with FP heatmaps on 158 (10.2%) and 307 (19.8%) of the 1548 normal mammograms. Conclusion Use of a standalone AI system improved early cancer detection by correctly identifying some cancers missed by two human readers, with no differences based on histopathologic features except for node-positive cancers. © RSNA, 2024 Supplemental material is available for this article.

Breast density effect on the sensitivity of digital screening mammography in a UK cohort.

OBJECTIVES: To assess the performance of breast cancer screening by category of breast density and age in a UK screening cohort. METHODS: Raw full-field digital mammography data from a single site in the UK, forming a consecutive 3-year cohort of women aged 50 to 70 years from 2016 to 2018, were obtained retrospectively. Breast density was assessed using Volpara software. Examinations were grouped by density category and age group (50-60 and 61-70 years) to analyse screening performance. Statistical analysis was performed to determine the association between density categories and age groups. Volumetric breast density was assessed as a binary classifier of interval cancers (ICs) to find an optimal density threshold. RESULTS: Forty-nine thousand nine-hundred forty-eight screening examinations (409 screen-detected cancers (SDCs) and 205 ICs) were included in the analysis. Mammographic sensitivity, SDC/(SDC + IC), decreased with increasing breast density from 75.0% for density a (p = 0.839, comparisons made to category b), to 73.5%, 59.8% (p = 0.001), and 51.3% (p < 0.001) in categories b, c, and d, respectively. IC rates were highest in the densest categories with rates of 1.8 (p = 0.039), 3.2, 5.7 (p < 0.001), and 7.9 (p < 0.001) per thousand for categories a, b, c, and d, respectively. The recall rate increased with breast density, leading to more false positive recalls, especially in the younger age group. There was no significant difference between the optimal density threshold found, 6.85, and that Volpara defined as the b/c boundary, 7.5. CONCLUSIONS: The performance of screening is significantly reduced with increasing density with IC rates in the densest category four times higher than in women with fatty breasts. False positives are a particular issue for the younger subgroup without prior examinations. CLINICAL RELEVANCE STATEMENT: In women attending screening there is significant underdiagnosis of breast cancer in those with dense breasts, most marked in the highest density category but still three times higher than in women with fatty breasts in the second highest category. KEY POINTS: Breast density can mask cancers leading to underdiagnosis on mammography. Interval cancer rate increased with breast density categories 'a' to 'd'; 1.8 to 7.9 per thousand. Recall rates increased with increasing breast density, leading to more false positive recalls.

Mammography Breast Cancer Screening Triage Using Deep Learning: A UK Retrospective Study.

Background Breast screening enables early detection of cancers; however, most women have normal mammograms, resulting in repetitive and resource-intensive reading tasks. Purpose To investigate if deep learning (DL) algorithms can be used to triage mammograms by identifying normal results to reduce workload or flag cancers that may be overlooked. Materials and Methods In this retrospective study, three commercial DL algorithms were investigated using consecutive mammograms from two UK Breast Screening Program sites from January 2015 to December 2017 and January 2017 to December 2018 on devices from two mammography vendors. Normal mammograms with a 3-year follow-up and histopathologically proven cancer detected at screening, the subsequent round, or in the 3-year interval were included. Two algorithm thresholds were set: in scenario A, 99.0% sensitivity for rule-out triage to a lone reader, and in scenario B, approximately 1.0% additional recall providing a rule-in triage for further assessment. Both thresholds were then applied to the screening workflow in scenario C. The sensitivity and specificity were used to assess the overall predictive performance of each DL algorithm. Results The data set comprised 78 849 patients (median age, 59 years [IQR, 53-63 years]) and 887 screening-detected, 439 interval, and 688 subsequent screening round-detected cancers. In scenario A (rule-out triage), models DL-1, DL-2, and DL-3 triaged 35.0% (27 565 of 78 849), 53.2% (41 937 of 78 849), and 55.6% (43 869 of 78 849) of mammograms, respectively, with 0.0% (0 of 887) to 0.1% (one of 887) of screening-detected cancers undetected. In scenario B, DL algorithms triaged in 4.6% (20 of 439) to 8.2% (36 of 439) of interval and 5.2% (36 of 688) to 6.1% (42 of 688) of subsequent-round cancers when applied after the routine double-reading workflow. Combining both approaches in scenario C resulted in an overall noninferior specificity (difference, -0.9%; P < .001) and superior sensitivity (difference, 2.7%; P < .001) for the adaptive workflow compared with routine double reading for all three algorithms. Conclusion Rule-out and rule-in DL-adapted triage workflows can improve the efficiency and efficacy of mammography breast cancer screening. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Nishikawa and Lu in this issue.

Adsorption of Fibronectin Fragment on Surfaces Using Fully Atomistic Molecular Dynamics Simulations.

The effect of surface chemistry on the adsorption characteristics of a fibronectin fragment (FNIII8⁻10) was investigated using fully atomistic molecular dynamics simulations. Model surfaces were constructed to replicate self-assembled monolayers terminated with methyl, hydroxyl, amine, and carboxyl moieties. It was found that adsorption of FNIII8⁻10 on charged surfaces is rapid, specific, and driven by electrostatic interactions, and that the anchoring residues are either polar uncharged or of opposing charge to that of the targeted surfaces. On charged surfaces the presence of a strongly bound layer of water molecules and ions hinders FNIII8⁻10 adsorption. In contrast, adsorption kinetics on uncharged surfaces are slow and non-specific, as they are driven by van der Waals interactions, and the anchoring residues are polar uncharged. Due to existence of a positively charged area around its cell-binding region, FNIII8⁻10 is available for subsequent cell binding when adsorbed on a positively charged surface, but not when adsorbed on a negatively charged surface. On uncharged surfaces, the availability of the fibronectin fragment's cell-binding region is not clearly distinguished because adsorption is much less specific.

Charge Awareness Affects Treatment Choice: Prospective Randomized Trial in Pediatric Appendectomy.

OBJECTIVE: To determine whether charge awareness affects patient decisions. BACKGROUND: Pediatric uncomplicated appendicitis can be treated with open or laparoscopic techniques. These 2 operations are considered to have clinical equipoise. METHODS: In a prospective, randomized clinical trial, nonobese children admitted to a children's hospital with uncomplicated appendicitis were randomized to view 1 of 2 videos discussing open and laparoscopic appendectomy. Videos were identical except that only one presented the difference in surgical materials charges. Patients and parents then choose which operation they desired. Videos were available in English and Spanish. A postoperative survey was conducted to examine factors that influenced choice. The trial was registered at ClinicalTrials.gov (NCT 01738750). RESULTS: Of 275 consecutive cases, 100 met enrollment criteria. In the group exposed to charge data (n = 49), 63% chose open technique versus 35% not presented charge data (P = 0.005). Patients were 1.8 times more likely to choose the less expensive option when charge estimate was given (95% confidence interval, 1.17-2.75). The median total hospital charges were $1554 less for those who had open technique (P < 0.001) and $528 less for the group exposed to charge information (P = 0.033). Survey found that 90% of families valued having input in this decision and 31% of patients exposed to charge listed it as their primary reason for their choice in technique. CONCLUSIONS: Patients and parents tended to choose the less expensive but equally effective technique when given the opportunity. A discussion of treatment options, which includes charge information, may represent an unrealized opportunity to affect change in health care spending.

Mammographic breast density: comparison of methods for quantitative evaluation.

PURPOSE: To evaluate the results from two software tools for measurement of mammographic breast density and compare them with observer-based scores in a large cohort of women. MATERIALS AND METHODS: Following written informed consent, a data set of 36 281 mammograms from 8867 women were collected from six United Kingdom centers in an ethically approved trial. Breast density was assessed by one of 26 readers on a visual analog scale and with two automated density tools. Mean differences were calculated as the mean of all the individual percentage differences between each measurement for each case (woman). Agreement in total breast volume, fibroglandular volume, and percentage density was assessed with the Bland-Altman method. Association with observer's scores was calculated by using the Pearson correlation coefficient (r). RESULTS: Correlation between the Quantra and Volpara outputs for total breast volume was r = 0.97 (P < .001), with a mean difference of 43.5 cm(3) for all cases representing 5.0% of the mean total breast volume. Correlation of the two measures was lower for fibroglandular volume (r = 0.86, P < .001). The mean difference was 30.3 cm(3) for all cases representing 21.2% of the mean fibroglandular tissue volume result. Quantra gave the larger value and the difference tended to increase with volume. For the two measures of percentage volume density, the mean difference was 1.61 percentage points (r = 0.78, P < .001). Comparison of observer's scores with the area-based density given by Quantra yielded a low correlation (r = 0.55, P < .001). Correlations of observer's scores with the volumetric density results gave r values of 0.60 (P < .001) and 0.63 (P < .001) for Quantra and Volpara, respectively. CONCLUSION: Automated techniques for measuring breast density show good correlation, but these are poorly correlated with observer's scores. However automated techniques do give different results that should be considered when informing patient personalized imaging. (©) RSNA, 2015 Clinical trial registration no. ISRCTN 73467396.

Design of an Optically Controlled MR-Compatible Active Needle.

An active needle is proposed for the development of magnetic resonance imaging (MRI)-guided percutaneous procedures. The needle uses a low-transition-temperature shape memory alloy (LT SMA) wire actuator to produce bending in the distal section of the needle. Actuation is achieved with internal optical heating using laser light transported via optical fibers and side coupled to the LT SMA. A prototype, with a size equivalent to a standard 16-gauge biopsy needle, exhibits significant bending, with a tip deflection of more than 14° in air and 5° in hard tissue. A single-ended optical sensor with a gold-coated tip is developed to measure the curvature independently of temperature. The experimental results in tissue phantoms show that human tissue causes fast heat dissipation from the wire actuator; however, the active needle can compensate for typical targeting errors during prostate biopsy.

Case report: Sodium dichloroacetate (DCA) inhibition of the "Warburg Effect" in a human cancer patient: complete response in non-Hodgkin's lymphoma after disease progression with rituximab-CHOP.

The uptake of fluorodeoxyglucose Positron Emission Tomography in the tumors of various cancer types demonstrates the key role of glucose in the proliferation of cancer. Dichloroacetate is a 2-carbon molecule having crucial biologic activity in altering the metabolic breakdown of glucose to lactic acid. Human cell line studies show that dichloroacetate switches alter the metabolomics of the cancer cell from one of glycolysis to oxidative phosphorylation, and in doing so restore mitochondrial functions that trigger apoptosis of the cancer cell. Reports of dichloroacetate in human subjects are rare. The authors contacted individuals from Internet forums who had reported outstanding anti-cancer responses to self-medication with dichloroacetate. With informed consent, complete medical records were requested to document response to dichloroacetate, emphasizing the context of monotherapy with dichloroacetate. Of ten patients agreeing to such an evaluation, only one met the criteria of having comprehensive clinic records as well as pathology, imaging and laboratory reports, along with single agent therapy with dichloroacetate. That individual is the focus of this report. In this case report of a man with documented relapse after state-of-the-art chemotherapy for non-Hodgkin's lymphoma, a significant response to dichloroacetate is documented with a complete remission, which remains ongoing after 4 years. Dichloroacetate appears to be a novel therapy warranting further investigation in the treatment of cancer.

Optimized 18F-FDG PET-CT Method to Improve Accuracy of Diagnosis of Metastatic Cancer.

The diagnosis of cancer by FDG PET-CT is often inaccurate owing to subjectivity of interpretation. We compared the accuracy of a novel normalized (standardized) method of interpretation with conventional non-normalized SUV. Patients (n = 393) with various malignancies were studied with FDG PET/CT to determine the presence or absence of cancer. Target lesions were assessed by two methods: (1) conventional SUVmax (conSUVmax) and (2) a novel method that combined multiple factors to optimize SUV (optSUVmax), including the patient's normal liver SUVmax, a liver constant (k) derived from a review of the literature, and use of site-specific thresholds for malignancy. The two methods were compared to pathology findings in 154 patients being evaluated for mediastinal and/or hilar lymph node (MHLNs) metastases, 143 evaluated for extra-thoracic lymph node (ETLNs) metastases, and 96 evaluated for liver metastases. OptSUVmax was superior to conSUVmax for all patient groups. For MHLNs, sensitivity was 83.8% vs. 80.7% and specificity 88.7% vs. 9.6%, respectively; for ETLNs, sensitivity was 92.1% vs. 77.8% and specificity 80.1% vs. 27.6%, respectively; and for lesions in the liver parenchyma, sensitivity was 96.1% vs. 82.3% and specificity 88.8% vs. 23.0%, respectively. Optimized SUVmax increased diagnostic accuracy of FDG PET-CT for cancer when compared with conventional SUVmax interpretation.

Three-dimensional biofabrication of nanosecond laser micromachined nanofibre meshes for tissue engineered scaffolds.

There is a high demand for bespoke grafts to replace damaged or malformed bone and cartilage tissue. Three-dimensional (3D) printing offers a method of fabricating complex anatomical features of clinically relevant sizes. However, the construction of a scaffold to replicate the complex hierarchical structure of natural tissues remains challenging. This paper reports a novel biofabrication method that is capable of creating intricately designed structures of anatomically relevant dimensions. The beneficial properties of the electrospun fibre meshes can finally be realised in 3D rather than the current promising breakthroughs in two-dimensional (2D). The 3D model was created from commercially available computer-aided design software packages in order to slice the model down into many layers of slices, which were arrayed. These 2D slices with each layer of a defined pattern were laser cut, and then successfully assembled with varying thicknesses of 100 µm or 200 µm. It is demonstrated in this study that this new biofabrication technique can be used to reproduce very complex computer-aided design models into hierarchical constructs with micro and nano resolutions, where the clinically relevant sizes ranging from a simple cube of 20 mm dimension, to a more complex, 50 mm-tall human ears were created. In-vitro cell-contact studies were also carried out to investigate the biocompatibility of this hierarchal structure. The cell viability on a micromachined electrospun polylactic-co-glycolic acid fibre mesh slice, where a range of hole diameters from 200 µm to 500 µm were laser cut in an array where cell confluence values of at least 85% were found at three weeks. Cells were also seeded onto a simpler stacked construct, albeit made with micromachined poly fibre mesh, where cells can be found to migrate through the stack better with collagen as bioadhesives. This new method for biofabricating hierarchical constructs can be further developed for tissue repair applications such as maxillofacial bone injury or nose/ear cartilage replacement in the future.

Migration drivers and migration choice: interrogating responses to migration and development interventions in West Africa.

The notion of migration as being at least partly about 'choice' is deeply rooted in both academic thought and public policy. Recent contributions have considered migration choice as step-wise in nature, involving a separation between 'aspiration' and 'ability' to migrate, whilst stressing a range of non-economic factors that influence migration choices. But such nuances have not prevented the emergence of a significant area of public policy that seeks to influence choices to migrate from Africa through 'irregular' channels, or at all, through a range of development interventions. This paper explores evidence from West Africa on how young people formulate the boundaries of such choice. Drawing on approaches in anthropology and elsewhere that stress the value of a 'future-orientated' lens, we show how present uncertainty is a central framing that fundamentally limits the value of thinking about migration as a choice. This has important implications for policy on 'migration and development'.

Studies on transannulation reactions across a nine-membered ring: the synthesis of natural product-like structures.

A series of diverse natural product-like structures have been synthesised by the use of a number of novel transannulation reactions across a cyclononene ring. Transannular cyclisations through oxygen functionality have generated a number of bicyclo[5.3.1]systems containing bridged cyclic ethers and bicyclo[5.2.2]lactones, as well as a tetrahydrofuran-containing bridged analogue of hexacyclinic acid. An unprecedented Brønsted acid mediated transannular cyclisation between proximal carbons generated bicyclo[4.3.0]nonanes which form the core of the pinguisane and austrodorane families of sesquiterpenoids. In all cases the key factor that determined the mode of reactivity was the conformation of the nine-membered ring and the distance between the reacting centres.

An improved process for the fabrication and surface treatment of custom-made titanium cranioplasty implants informed by surface analysis.

Cranioplasty implants are routinely fabricated from commercially pure titanium plates by maxillofacial prosthetists. The differing fabrication protocols adopted by prosthetists working at different hospital sites gives rise to considerable variations in surface topography and composition of cranioplasty implants, with residues from the fabrication processes having been found to become incorporated into the surface of the implant. There is a growing recognition among maxillofacial prosthetists of the need to standardise these protocols to ensure quality and consistency of practice within the profession. In an effort to identify and eliminate the source of the inclusions associated with one such fabrication protocol, the present study examined the surfaces of samples subjected to each of the manufacturing steps involved. Surface and elemental analysis techniques identified the main constituent of the surface inclusions to be silicon from the glass beads used to texture the surface of the implant during fabrication. Subsequent analysis of samples prepared according to a revised protocol resulted in a more homogeneous titanium dioxide surface as evidenced by the reduction in area occupied by surface inclusions (from 8.51% ± 2.60% to 0.93% ± 0.62%). These findings may inform the development of improved protocols for the fabrication of titanium cranioplasty plates.

A Progressive Nutrient Profiling System to Guide Improvements in Nutrient Density of Foods and Beverages.

Improving the nutrient density of processed foods is one way to bring the global food supply closer to the WHO Sustainable Development Goals. Nutrient profiling (NP) has emerged as the preferred method of monitoring the progress toward product innovation and reformulation. This paper presents PepsiCo Nutrition Criteria (PNC), a new internal NP model that was designed to guide and monitor improvements in nutrient density and overall nutritional quality of foods and beverages. The new PNC NP model assigns food products into four classes of increasing nutritional value, based on the content of nutrients to limit, along with nutrients and ingredients to encourage. The nutrient standards used for category assignment followed those developed by global dietary authorities. Standards are proposed for calories, sodium, added sugars, saturated, and industrially produced trans fats. Also included are minimum values for food groups to encourage, low-fat dairy, and for country-specific gap nutrients. Internal use of the NP model has spurred product changes that are consistent with WHO goals for industry transparency. An audited review of company products showed that 48% met added sugar, 65% met sodium, and 71% met saturated fat goals. By the end of 2020, in the top 26 regions in which products are sold, 48% of the total sales volume of global beverages had 100 kcal or less from added sugars per 355 ml serving representing 80% of beverage volume and over 90% of food volume sold globally. The PNC NP model is not consumer-facing but is specifically intended for internal use to motivate stepwise and incremental product innovation and reformulation. Transparent and published NP models further WHO goals of engaging industry stakeholders in the (re)formulation of processed foods and beverages consistent with public health goals.

Coffee mannooligosaccharides, consumed as part of a free-living, weight-maintaining diet, increase the proportional reduction in body volume in overweight men.

Clinical studies have shown that the consumption of coffee mannooligosaccharides (MOS) decreases body fat, suggesting that MOS consumption may be useful for weight management. This study was undertaken to determine whether consumption of coffee MOS improves body composition when consumed as part of a weight-maintaining diet. In this double-blind, randomized, placebo-controlled study, 54 men and women, age 19-65 y and with BMI of 27-33 kg/m(2), consumed study beverages twice daily, for 12 wk. Beverages were identical except for the presence (MOS group) or absence (placebo group) of MOS (4 g/d). Body composition was assessed at baseline and endpoint using magnetic resonance imaging (MRI). Body weight, blood pressure, and assessments of feelings of appetite and satiety were taken weekly. Fifty men and women completed both baseline and endpoint MRI scans. There was a significant beverage x time interaction on total body volume (P = 0.026), total adipose tissue (TAT) (P = 0.046), and total subcutaneous adipose tissue (P = 0.032) in men but not women. Men consuming the MOS beverage had a greater percent change in total body volume (P = 0.043) and tended to have greater percent changes in subcutaneous (P = 0.069) and TAT (P = 0.098) compared with the placebo group. Consumption of a MOS-containing beverage, as part of a free-living weight-maintaining diet, leads to reductions in total body volume, relative to placebo, in men. More research is needed to further investigate the mechanism by which MOS may act to improve body composition and to elucidate the influence of gender.

Real-Time Estimation of 3-D Needle Shape and Deflection for MRI-Guided Interventions.

We describe a MRI-compatible biopsy needle instrumented with optical fiber Bragg gratings for measuring bending deflections of the needle as it is inserted into tissues. During procedures, such as diagnostic biopsies and localized treatments, it is useful to track any tool deviation from the planned trajectory to minimize positioning errors and procedural complications. The goal is to display tool deflections in real time, with greater bandwidth and accuracy than when viewing the tool in MR images. A standard 18 ga × 15 cm inner needle is prepared using a fixture, and 350-µm-deep grooves are created along its length. Optical fibers are embedded in the grooves. Two sets of sensors, located at different points along the needle, provide an estimate of the bent profile, as well as temperature compensation. Tests of the needle in a water bath showed that it produced no adverse imaging artifacts when used with the MR scanner.

Low-Cost Eye Phantom for Stereophotogrammetry-Based Optic Nerve Head Topographical 3D Imaging.

Glaucoma is the second leading cause of blindness globally. Stereophotogrammetry-based optic nerve head topographical imaging systems could potentially allow for objective glaucoma assessment in settings where technologies such as optical coherence tomography and the Heidelberg Retinal Tomograph are prohibitively expensive. In the development of such systems, eye phantoms are invaluable tools for both system calibration and performance evaluation. Eye phantoms developed for this purpose need to replicate the optical configuration of the eye, the related causes of measurement artefacts, and give the possibility to present to the imaging system the targets required for system calibration. The phantoms in the literature that show promise of meeting these requirements rely on custom lenses to be fabricated, making them very costly. Here, we propose a low-cost eye phantom comprising a vacuum formed cornea and commercially available stock bi-convex lens, that is optically similar to a gold-standard reference wide-angle schematic eye model and meets all the compliance and configurability requirements for use with stereo-photogrammetry-based ONH topographical imaging systems. Moreover, its modular design, being fabricated largely from 3D-printed components, lends itself to modification for other applications. The use of the phantom is successfully demonstrated in an ONH imager.

Probing fibronectin adsorption on chemically defined surfaces by means of single molecule force microscopy.

Atomic force microscope (AFM) based single molecule force spectroscopy (SMFS) and a quartz crystal microbalance (QCM) were respectively employed to probe interfacial characteristics of fibronectin fragment FNIII8-14 and full-length fibronectin (FN) on CH3-, OH-, COOH-, and NH2-terminated alkane-thiol self-assembled monolayers (SAMs). Force-distance curves acquired between hexahistidine-tagged FNIII8-14 immobilised on trisNTA-Ni2+ functionalized AFM cantilevers and the OH and COOH SAM surfaces were predominantly 'loop-like' (76% and 94% respectively), suggesting domain unfolding and preference for 'end-on' oriented binding, while those generated with NH2 and CH3 SAMs were largely 'mixed type' (81% and 86%, respectively) commensurate with unravelling and desorption, and 'side-on' binding. Time-dependent binding of FN to SAM-coated QCM crystals occurred in at least two phases: initial rapid coverage over the first 5 min; and variably diminishing adsorption thereafter (5-70 min). Loading profiles and the final hydrated surface concentrations reached (~ 950, ~ 1200, ~ 1400, ~ 1500 ng cm-2 for CH3, OH, COOH and NH2 SAMs) were consistent with: space-filling 'side-on' orientation and unfolding on CH3 SAM; greater numbers of FN molecules arranged 'end-on' on OH and especially COOH SAMs; and initial 'side-on' contact, followed by either (1) gradual tilting to a space-saving 'end-on' configuration, or (2) bi-/multi-layer adsorption on NH2 SAM.