Diagnostic Performance and Clinical Impact of PSMA PET/CT versus mpMRI in Patients with a High Suspicion of Prostate Cancer and Previously Negative Biopsy: A Prospective Trial (PROSPET-BX).

BACKGROUND: This prospective single-arm study is designed to compare in parallel 68Ga-PSMA PET/TRUS (transrectal or transperineal) fusion biopsy ("experimental test") with multiparametric MRI (mpMRI)/TRUS fusion prostate biopsy ("standard test") in men with a high suspicion of prostate cancer (PCa) after at least one negative biopsy. The primary objective was to evaluate the diagnostic performance of 68Ga-PSMA PET/TRUS fusion prostate biopsy in comparison to mpMRI/TRUS fusion prostate biopsy analyzed in parallel. Secondarily, we aimed to determine the relationship between the "experimental test" and the histopathological characteristics of the specimen, along with the clinical utility of the "experimental test" compared to the "standard test." SUMMARY: To test the superiority of 68Ga-PSMA PET/CT compared to mpMRI, we will enroll a minimum cohort of 128 patients. Inclusion criteria comprise: age >18 years; blood PSA level >4.0 ng/mL; free-to-total PSA ratio <20%; progressive rise of PSA levels in two consecutive blood samples despite antibiotics; serum blood tests suspicious for PCa; at least one previous negative biopsy; ASAP and/or high-grade PIN; negative digital rectal examination. All eligible patients will undergo 68Ga-PSMA PET/CT and mpMRI scans within 1 month's distance from each other, followed by biopsy session to be completed within 1 month's distance. Targeted TRUS fusion needle biopsy will be performed for all lesions detected with PET and mpMRI. The total duration of the study is 36 months. KEY MESSAGES: By comparing the "experimental test" and the "standard test" in parallel, we will be able to determine the superior diagnostic performance of 68Ga-PSMA PET/CT over mpMRI in detecting PCa, and in particular clinically significant PCa, in the specific cohort of patients with a high suspicion of PCa who are candidates to re-biopsy. The clinical impact of the "experimental test" will be subsequently analyzed in terms of the number of prostate biopsies that could be spared, time-consuming, patient friendliness, and cost-effectiveness.

DXA-derived lumbar bone strain index corrected for kyphosis is associated with vertebral fractures and trabecular bone score in acromegaly.

PURPOSE: The bone strain index (BSI) is a marker of bone deformation based on a finite element analysis inferred from dual X-ray absorptiometry (DXA) scans, that has been proposed as a predictor of fractures in osteoporosis (i.e., higher BSI indicates a lower bone's resistance to loads with consequent higher risk of fractures). We aimed to investigate the association between lumbar BSI and vertebral fractures (VFs) in acromegaly. METHODS: Twenty-three patients with acromegaly (13 males, mean age 58 years; three with active disease) were evaluated for morphometric VFs, trabecular bone score (TBS), bone mineral density (BMD) and BSI at lumbar spine, the latter being corrected for the kyphosis as measured by low-dose X-ray imaging system (EOS®-2D/3D). RESULTS: Lumbar BSI was significantly higher in patients with VFs as compared to those without fractures (2.90 ± 1.46 vs. 1.78 ± 0.33, p = 0.041). BSI was inversely associated with TBS (rho -0.44; p = 0.034), without significant associations with BMD (p = 0.151), age (p = 0.500), BMI (p = 0.957), serum IGF-I (p = 0.889), duration of active disease (p = 0.434) and sex (p = 0.563). CONCLUSIONS: Lumbar BSI corrected for kyphosis could be proposed as integrated parameter of spine arthropathy and osteopathy in acromegaly helping the clinicians in identifying patients with skeletal fragility possibly predisposed to VFs.

Prevalence and determinants of radiological vertebral fractures in patients with Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (KS) may induce skeletal fragility, but the studies so far published on this topic were mainly focused on the evaluation of bone mineral density (BMD) and bone microstructure, whereas data on fracture risk are still lacking. OBJECTIVE: To evaluate the prevalence and determinants of vertebral fractures (VFs), that is, the hallmark of osteoporosis, in subjects with KS. MATERIALS AND METHODS: Eighty-seven patients with KS (median age 41 years, range 18-64) were consecutively evaluated for radiological VFs (by quantitative morphometry) and lumbar spine and femoral neck BMD (by DXA). Fifty-five patients with KS were also evaluated by the fracture risk assessment (FRAX) tool. RESULTS: Low BMD was found in 22/87 (25.3%) patients [12 with osteopenia, three with osteoporosis and seven with "low BMD per age" (subject < 50 years with Z-score ≤-2.0 SD)] and VFs in 13/87 (14.9%) patients. In patients with VFs, the median spine deformity index was 2 (range 1-9). Prevalence of VFs was similar between healthy and low-BMD patients (15.9% vs 13.6%; P = .80). Noteworthy, patients with VFs had significantly higher age at diagnosis of KS as compared to patients who did not fracture (P = .039), without significant differences in age at the time of observation (P = .162), body mass index (P = .234), testosterone replacement therapy (P = .432), duration of testosterone therapy (P = .409), vitamin D therapy (P = 681), and serum testosterone levels (P = .338). Moreover, patients with VFs were more likely to complain back pain in comparison with those without VFs (33.3% vs 7.4%; P = .047). In 55 cases evaluated by the FRAX® tool, no significant differences in 10-year risk of major fracture (P = .270) and hip fracture (P = .860) were found between fractured and non-fractured patients. CONCLUSIONS: This study provides first evidence that KS may be associated with risk of VFs in close relationship with delay in disease diagnosis but independently of BMD values and serum testosterone levels or testosterone therapy.

Rapid tissue viability evaluation using methemoglobin as a biomarker in burns.

Burns are a frequent cause of traumatic injury, accounting for an average of 1,230 visits to the emergency department every day in the United States. While many of these injuries will heal spontaneously, nearly 1 in 10 are severe enough to require hospitalization or transfer to a specialized burn center. The early surgical management of a severe burn is critical to patient outcome, but few tools exist for triaging viable and non-viable tissue at early time-points post-injury. Without a validated outcome measure, even experienced burn surgeons diagnose tissue viability with an accuracy of only 50-70%, with significant consequences for patient morbidity, mortality and cost to the healthcare system. In this work, we have developed a non-invasive device that uses near-infrared spectroscopy to rapidly assess traumatic burns at the bedside. We report that near-infrared spectroscopy can detect methemoglobin non-invasively, and that this molecule increases in burned tissue immediately following injury in both a porcine model and in humans. Methemoglobin levels are highest in non-viable tissue, and correlate with tissue viability as early as 24 hours post-burn. Methemoglobin is the first reported objective outcome measure for use in the management of traumatic burn injury.

FDG PET/CT as theranostic imaging in diagnosis of non-small cell lung cancer.

Objective of this work was to evaluate the role of 18F-fluorodeoxyglucose (FDG) positron-emission tomography features as theranostic imaging biomarkers in non-small cell lung cancer. In a retrospective protocol, 31 stage I-III NSCLC patients were enrolled. Patients underwent FDG PET/CT for staging purposes before surgery and were followed for two years after surgery. PET images were quantitatively analyzed. For the primary lesion, metabolic tumour volume, maximum standardized uptake value (SUV), SUV corrected for partial volume effect, total lesion glycolysis, 14 histogram and four shape-and-size features were extracted as PET imaging features. PET features were correlated with histology and 2-year disease-free survival (DFS). Significant correlations were found between grading, T parameter, N status, pathological stage and different FDG PET features. Histogram-based features "energy" and "kurtosis" resulted to be predictive for DFS. The cut-off value identified for "kurtosis" was able to separate the adenocarcinoma patients with different outcomes. FDG PET features are able to characterize lung cancer lesions, suggesting the possibility of reliable "imaging biopsy", and have a predictive role in adenocarcinoma patients undergoing surgery.

Targeted 11C-choline PET-CT/TRUS software fusion-guided prostate biopsy in men with persistently elevated PSA and negative mpMRI after previous negative biopsy.

BACKGROUND: We evaluated the feasibility and accuracy of 11C-choline PET-CT/TRUS fusion-guided prostate biopsy in men with persistently elevated PSA and negative mpMRI or contraindication to MRI, after previous negative biopsy. Clinical data were part of a prospective on-going observational clinical study: "Diagnostic accuracy of target mpMRI/US fusion biopsy in patients with suspected prostate cancer after initial negative biopsy". Patients with a negative biopsy and negative mpMRI (PI-RADS v.2 < 3) or absolute contraindications to MRI and persistently elevated PSA, were included. All patients underwent 11C-choline PET with dedicated acquisition of the pelvis and PET-CT/TRUS-guided prostate biopsy by Bio-Jet™ fusion system (D&K Technologies, Germany). The primary endpoint was to assess the accuracy of 11C-choline PET-CT to determine the presence and the topographical distribution of PCa. RESULTS: Overall, 15 patients (median age 71 yrs. ± 8.89; tPSA 13.5 ng/ml ± 4.3) were analysed. Fourteen had a positive PET scan, which revealed 30 lesions. PCa was detected in 7/15 patients (46.7%) and four patients presented a clinically significant PCa: GS > 6. Over 58 cores, 25 (43.1%) were positive. No statistically significant difference in terms of mean and median values for SUVmax and SUVratio between benign and malignant lesions was found. PCa lesions with GS 3 + 3 (n = 3) showed a median SUVmax and SUVratio of 4.01 and 1.46, compared to 5.45 and 1.57, respectively for lesions with GS >6 (n = 4). CONCLUSION: Software PET-CT/TRUS fusion-guided target biopsy could be a diagnostic alternative in patients with a suspected primary PCa and negative mpMRI, but its specificity appeared low.

Classification of burn injuries using near-infrared spectroscopy.

Early surgical management of those burn injuries that will not heal spontaneously is critical. The decision to excise and graft is based on a visual assessment that is often inaccurate but yet continues to be the primary means of grading the injury. Superficial and intermediate partial-thickness injuries generally heal with appropriate wound care while deep partial- and full-thickness injuries generally require surgery. This study explores the possibility of using near-infrared spectroscopy to provide an objective and accurate means of distinguishing shallow injuries from deeper burns that require surgery. Twenty burn injuries are studied in five animals, with burns covering <1% of the total body surface area. Carefully controlled superficial, intermediate, and deep partial-thickness injuries as well as full-thickness injuries could be studied with this model. Near-infrared reflectance spectroscopy was used to evaluate these injuries 1 to 3 hours after the insult. A probabilistic model employing partial least-squares logistic regression was used to determine the degree of injury, shallow (superficial or intermediate partial) from deep (deep partial and full thickness), based on the reflectance spectrum of the wound. A leave-animal-out cross-validation strategy was used to test the predictive ability of a 2-latent variable, partial least-squares logistic regression model to distinguish deep burn injuries from shallow injuries. The model displayed reasonable ranking quality as summarized by the area under the receiver operator characteristics curve, AUC = 0.879. Fixing the threshold for the class boundaries at 0.5 probability, the model sensitivity (true positive fraction) to separate deep from shallow burns was 0.90, while model specificity (true negative fraction) was 0.83. Using an acute porcine model of thermal burn injuries, the potential of near-infrared spectroscopy to distinguish between shallow healing burns and deeper burn injuries was demonstrated. While these results should be considered as preliminary and require clinical validation, a probabilistic model capable of differentiating these classes of burns would be a significant aid to the burn specialist.

Ex vivo detection and characterization of early dental caries by optical coherence tomography and Raman spectroscopy.

Early dental caries detection will facilitate implementation of nonsurgical methods for arresting caries progression and promoting tooth remineralization. We present a method that combines optical coherence tomography (OCT) and Raman spectroscopy to provide morphological information and biochemical specificity for detecting and characterizing incipient carious lesions found in extracted human teeth. OCT imaging of tooth samples demonstrated increased light backscattering intensity at sites of carious lesions as compared to the sound enamel. The observed lesion depth on an OCT image was approximately 290 microm matching those previously documented for incipient caries. Using Raman microspectroscopy and fiber-optic-based Raman spectroscopy to characterize the caries further, spectral changes were observed in PO4 (3-) vibrations arising from hydroxyapatite of mineralized tooth tissue. Examination of various ratios of PO4 (3-) nu2, nu3, nu4 vibrations against the nu1 vibration showed consistent increases in carious lesions compared to sound enamel. The changes were attributed to demineralization-induced alterations of enamel crystallite morphology and/or orientation. OCT imaging is useful for screening carious sites and determining lesion depth, with Raman spectroscopy providing biochemical confirmation of caries. The combination has potential for development into a new fiber-optic diagnostic tool enabling dentists to identify early caries lesions with greater sensitivity and specificity.

Imaging struma ovarii by means of 124I-Na PET/CT.

Struma ovarii is a rare form of ovary tumour defined as the presence of ectopic thyroid tissue in the ovarian structures. It usually presents with a benign course, although in some cases carcinoma or other malignant tumours can be found in the context of the ectopic tissue. Herein we report the case of a young patient affected by struma ovarii visualized by means of 124I-NaPET/CT. Thanks to the excellent target-to-background ratio of the tracer and the high resolution of the method, we could well identify the presence of some minimal tumour at the level of the left ovary. To our knowledge, this is the first report of its kind.

Noninvasive measurement of edema in partial thickness burn wounds.

A lack of noninvasive tools to quantify edema has limited our understanding of burn wound edema pathophysiology in a clinical setting. Near-infrared spectroscopy (NIR) is a new noninvasive tool able to measure water concentration/edema in tissue. The purpose of this study was to determine whether NIR could detect water concentration changes or edema formation in acute partial-thickness burn injuries. Adult burn patients within 72 hours postinjury, thermal etiology, partial-thickness burn depth, and <20% TBSA were included. Burn wounds were stratified into partial-thickness superficial or deep wounds based on histology and wound healing time. NIR devices were used to quantify edema in a burn and respective control sites. The sample population consisted of superficial (n = 12) and deep (n = 5) partial-thickness burn injuries. The patients did not differ with respect to age (40 +/- 15 years), TBSA (5 +/- 4%), and mean time for edema assessment (2 days). Water content increased 15% in burned tissue compared with the respective control regions. There were no differences in water content at the control sites. At 48 hours, deep partial-thickness injuries showed a 23% increase in water content compared with 18% superficial partial-thickness burns. NIR could detect differences in water content or edema formation in partial-thickness burns and unburned healthy regions. NIR holds promise as a noninvasive, portable clinical tool to quantify water content or edema in burn wounds.

Assessment of skin flaps using optically based methods for measuring blood flow and oxygenation.

The objective of this study was to compare two noninvasive techniques, laser Doppler and optical spectroscopy, for monitoring hemodynamic changes in skin flaps. Animal models for assessing these changes in microvascular free flaps and pedicle flaps were investigated. A 2 x 3-cm free flap model based on the epigastric vein-artery pair and a reversed MacFarlane 3 x 10-cm pedicle flap model were used in this study. Animals were divided into four groups, with groups 1 (n = 6) and 2 (n = 4) undergoing epigastric free flap surgery and groups 3 (n = 3) and 4 (n = 10) undergoing pedicle flap surgery. Groups 1 and 4 served as controls for each of the flap models. Groups 2 and 3 served as ischemia-reperfusion models. Optical spectroscopy provides a measure of hemoglobin oxygen saturation and blood volume, and the laser Doppler method measures blood flow. Optical spectroscopy proved to be consistently more reliable in detecting problems with arterial in flow compared with laser Doppler assessments. When spectroscopy was used in an imaging configuration, oxygen saturation images of the entire flap were generated, thus creating a visual picture of global flap health. In both single-point and imaging modes the technique was sensitive to vessel manipulation, with the immediate post operative images providing an accurate prediction of eventual outcome. This series of skin flap studies suggests a potential role for optical spectroscopy and spectroscopic imaging in the clinical assessment of skin flaps.