Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging reliably detect pelvic lymph node metastases in normal-sized nodes of bladder and prostate cancer patients

BACKGROUND: Lymph node staging of bladder or prostate cancer using conventional imaging is limited. Newer approaches such as ultrasmall superparamagnetic particles of iron oxide (USPIO) and diffusion-weighted magnetic resonance imaging (DW-MRI) have inconsistent diagnostic accuracy and are difficult to interpret. OBJECTIVE: To assess whether combined USPIO and DW-MRI (USPIO-DW-MRI) improves staging of normal-sized lymph nodes in bladder and/or prostate cancer patients. DESIGN, SETTING, AND PARTICIPANTS: Twenty-one consecutive patients with bladder and/or prostate cancer were enrolled between May and October 2008. One patient was excluded secondary to bone metastases detected on DW-MRI with subsequent abstention from surgery. INTERVENTION: Patients preoperatively underwent 3-T MRI before and after administration of lymphotropic USPIO using conventional MRI sequences combined with DW-MRI. Surgery consisted of extended pelvic lymphadenectomy and resection of primary tumors. MEASUREMENTS: Diagnostic accuracies of the new combined USPIO-DW-MRI approach compared with the "classic" reading method evaluating USPIO images without and with DW-MRI versus histopathology were evaluated. Duration of the two reading methods was noted for each patient. RESULTS AND LIMITATIONS: Diagnostic accuracy (90% per patient or per pelvic side) was comparable for the classic and the USPIO-DW-MRI reading method, while time of analysis with 80 min (range 45-180 min) for the classic and 13 min (range 5-90 min) for the USPIO-DW-MRI method was significantly shorter (p<0.0001). Interobserver agreement (three blinded readers) was high with a kappa value of 0.75 and 0.84, respectively. Histopathological analysis showed metastases in 26 of 802 analyzed lymph nodes (3.2%). Of these, 24 nodes (92%) were correctly diagnosed as positive on USPIO-DW-MRI. In two patients, one micrometastasis each (1.0x0.2 mm; 0.7x0.4 mm) was missed in all imaging studies. CONCLUSIONS: USPIO-DW-MRI is a fast and accurate method for detecting pelvic lymph node metastases, even in normal-sized nodes of bladder or prostate cancer patients.

Multimodal approach in the use of clinical scoring, morphological MRI and biochemical T2-mapping and diffusion-weighted imaging in their ability to assess differences between cartilage repair tissue after microfracture therapy and matrix-associated autologous chondrocyte transplantation: a pilot study

OBJECTIVE: The aim of the present pilot study is to show initial results of a multimodal approach using clinical scoring, morphological magnetic resonance imaging (MRI) and biochemical T2-relaxation and diffusion-weighted imaging (DWI) in their ability to assess differences between cartilage repair tissue after microfracture therapy (MFX) and matrix-associated autologous chondrocyte transplantation (MACT). METHOD: Twenty patients were cross-sectionally evaluated at different post-operative intervals from 12 to 63 months after MFX and 12-59 months after MACT. The two groups were matched by age (MFX: 36.0+/-10.4 years; MACT: 35.1+/-7.7 years) and post-operative interval (MFX: 32.6+/-16.7 months; MACT: 31.7+/-18.3 months). After clinical evaluation using the Lysholm score, 3T-MRI was performed obtaining the MR observation of cartilage repair tissue (MOCART) score as well as T2-mapping and DWI for multi-parametric MRI. Quantitative T2-relaxation was achieved using a multi-echo spin-echo sequence; semi-quantitative diffusion-quotient (signal intensity without diffusion-weighting divided by signal intensity with diffusion weighting) was prepared by a partially balanced, steady-state gradient-echo pulse sequence. RESULTS: No differences in Lysholm (P=0.420) or MOCART (P=0.209) score were observed between MFX and MACT. T2-mapping showed lower T2 values after MFX compared to MACT (P=0.039). DWI distinguished between healthy cartilage and cartilage repair tissue in both procedures (MFX: P=0.001; MACT: P=0.007). Correlations were found between the Lysholm and the MOCART score (Pearson: 0.484; P=0.031), between the Lysholm score and DWI (Pearson:-0.557; P=0.011) and a trend between the Lysholm score and T2 (Person: 0.304; P=0.193). CONCLUSION: Using T2-mapping and DWI, additional information could be gained compared to clinical scoring or morphological MRI. In combination clinical, MR-morphological and MR-biochemical parameters can be seen as a promising multimodal tool in the follow-up of cartilage repair.

Effect of vascular targeting agent in rat tumor model: dynamic contrast-enhanced versus diffusion-weighted MR imaging

PURPOSE: To compare dynamic contrast material-enhanced magnetic resonance (MR) imaging and diffusion-weighted MR imaging for noninvasive evaluation of early and late effects of a vascular targeting agent in a rat tumor model. MATERIALS AND METHODS: The study protocol was approved by the local ethics committee for animal care and use. Thirteen rats with one rhabdomyosarcoma in each flank (26 tumors) underwent dynamic contrast-enhanced imaging and diffusion-weighted echo-planar imaging in a 1.5-T MR unit before intraperitoneal injection of combretastatin A4 phosphate and at early (1 and 6 hours) and later (2 and 9 days) follow-up examinations after the injection. Histopathologic examination was performed at each time point. The apparent diffusion coefficient (ADC) of each tumor was calculated separately on the basis of diffusion-weighted images obtained with low b gradient values (ADC(low); b = 0, 50, and 100 sec/mm(2)) and high b gradient values (ADC(high); b = 500, 750, and 1000 sec/mm(2)). The difference between ADC(low) and ADC(high) was used as a surrogate measure of tissue perfusion (ADC(low) - ADC(high) = ADC(perf)). From the dynamic contrast-enhanced MR images, the volume transfer constant k and the initial slope of the contrast enhancement-time curve were calculated. For statistical analyses, a paired two-tailed Student t test and linear regression analysis were used. RESULTS: Early after administration of combretastatin, all perfusion-related parameters (k, initial slope, and ADC(perf)) decreased significantly (P < .001); at 9 days after combretastatin administration, they increased significantly (P < .001). Changes in ADC(perf) were correlated with changes in k (R(2) = 0.46, P < .001) and the initial slope (R(2) = 0.67, P < .001). CONCLUSION: Both dynamic contrast-enhanced MR imaging and diffusion-weighted MR imaging allow monitoring of perfusion changes induced by vascular targeting agents in tumors. Diffusion-weighted imaging provides additional information about intratumoral cell viability versus necrosis after administration of combretastatin.

Diffusion-weighted imaging of the parotid gland: Influence of the choice of b-values on the apparent diffusion coefficient value

PURPOSE: To determine how the ADC value of parotid glands is influenced by the choice of b-values. MATERIALS AND METHODS: In eight healthy volunteers, diffusion-weighted echo-planar imaging (DW-EPI) was performed on a 1.5 T system, with b-values (in seconds/mm2) of 0, 50, 100, 150, 200, 250, 300, 500, 750, and 1000. ADC values were calculated by two alternative methods (exponential vs. logarithmic fit) from five different sets of b-values: (A) all b-values; (B) b=0, 50, and 100; (C) b=0 and 750; (D) b=0, 500, and 1000; and (E) b=500, 750, and 1000. RESULTS: The mean ADC values for the different settings were (in 10(-3) mm2/second, exponential fit): (A) 0.732+/-0.019, (B) 2.074+/-0.084, (C) 0.947+/-0.020, (D) 0.890+/-0.023, and (E) 0.581+/-0.021. ADC values were significantly (P <0.001) different for all pairwise comparisons of settings (A-E) of b-values, except for A vs. D (P=0.172) and C vs. D (P=0.380). The ADC(B) was significantly higher than ADC(C) or ADC(D), which was significantly higher than ADC(E). ADC values from exponential vs. logarithmic fit (P=0.542), as well as left vs. right parotid gland (P=0.962), were indistinguishable. CONCLUSION: The ADC values calculated from low b-value settings were significantly higher than those calculated from high b-value settings. These results suggest that not only true diffusion but also perfusion and saliva flow may contribute to the ADC.

Noninvasive assessment of acute ureteral obstruction with diffusion-weighted MR imaging: a prospective study

PURPOSE: To prospectively assess the potential of noninvasive diffusion-weighted magnetic resonance (MR) imaging to depict changes in microperfusion and diffusion in patients with acute unilateral ureteral obstruction. MATERIALS AND METHODS: The local ethics committee approved the study protocol. Informed consent was obtained. Diffusion-weighted MR imaging was performed in 21 patients (two women, 19 men; mean age, 43 years +/- 10 [standard deviation]) with acute unilateral ureteral obstruction due to a calculus diagnosed at unenhanced computed tomography. A control group (one woman, 15 men; mean age, 44 years +/- 12) underwent the same MR protocol. Standard processing yielded an apparent diffusion coefficient (ADC) ADCT; the separation of microperfusion and diffusion contributions yielded the perfusion fraction FP and the pure diffusion coefficient ADCD. ADCT, ADCD, and FP were compared between obstructed and contralateral unobstructed kidneys and with control values. For statistical analysis, nonparametric rank tests were used. A P value of less than .05 was considered significant. RESULTS: No significant differences were observed between the ADCT of the medulla or cortex of the obstructed and unobstructed kidneys. Compared with control kidneys, only medullary ADCT was slightly increased in the obstructed kidney (P < .04). However, the ADCD in the medulla of the obstructed and unobstructed kidneys was significantly higher than that in control subjects (201 x 10(-5) mm2/sec +/- 16 and 199 x 10(-5) mm2/sec +/- 20 vs 189 x 10(-5) mm2/sec +/- 12; P < .008 and P < .03, respectively). FP of the cortex of the obstructed kidney was significantly lower than that in the unobstructed kidney (20.2% +/- 4.8 vs 24.0% +/- 5.8; P < .002); FP of the medulla was slightly lower in the obstructed kidney than in the unobstructed kidney (18.3% +/- 5.9 vs 20.7% +/- 6.4; P = .05). CONCLUSION: Diffusion-weighted MR imaging allows noninvasive detection of changes in renal perfusion and diffusion during acute unilateral ureteral obstruction, as exemplified in patients with a ureteral calculus.

Dynamic contrast-enhanced and diffusion-weighted MRI for early detection of tumoral changes in single-dose and fractionated radiotherapy: evaluation in a rat rhabdomyosarcoma model

We aimed to examine different intratumoral changes after single-dose and fractionated radiotherapy, using diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI in a rat rhabdomyosarcoma model. Four WAG/Rij rats with rhabdomyosarcomas in the flanks received single-dose radiotherapy of 8 Gy, and four others underwent fractionated radiotherapy (five times 3 Gy). In rats receiving single-dose radiotherapy, a significant perfusion decrease was found in the first 2 days post-treatment, with slow recuperation afterwards. No substantial diffusion changes could be seen; tumor growth delay was 12 days. The rats undergoing fractionated radiotherapy showed a similar perfusion decrease early after the treatment. However, a very strong increase in apparent diffusion coefficient occurred in the first 10 days; growth delay was 18 days. DW-MRI and DCE-MRI can be used to show early tumoral changes induced by radiotherapy. Single-dose and fractionated radiotherapy induce an immediate perfusion effect, while the latter induces more intratumoral necrosis.

Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses

OBJECTIVE: To evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses. STUDY DESIGN: Prospective, blinded, randomized cross-over study. ANIMALS: Ten healthy adult horses weighing 527-645 kg and aged 11-21 years old. METHODS: Electrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was recorded from the common digital extensor and the cranial tibial muscles. After baseline measurements a single bolus dose of detomidine, 0.02 mg kg(-1), romifidine 0.08 mg kg(-1), or xylazine, 1 mg kg(-1), was administered intravenously (IV). Determinations of NWR and temporal summation thresholds were repeated at 10, 20, 30, 40, 60, 70, 90, 100, 120 and 130 minutes after test-drug administration alternating the thoracic limb and the pelvic limb. Depth of sedation was assessed before measurements at each time point. Behavioural reaction was observed and recorded following each stimulation. RESULTS: The administration of detomidine, romifidine and xylazine significantly increased the current intensities necessary to evoke NWR and temporal summation in thoracic limbs and pelvic limbs of all horses compared with baseline. Xylazine increased NWR thresholds over baseline values for 60 minutes, while detomidine and romifidine increased NWR thresholds over baseline for 100 and 120 minutes, respectively. Temporal summation thresholds were significantly increased for 40, 70 and 130 minutes after xylazine, detomidine and romifidine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine, romifidine and xylazine, administered IV at doses considered equipotent for sedation, significantly increased NWR and temporal summation thresholds, used as a measure of antinociceptive activity. The extent of maximal increase of NWR and temporal summation thresholds was comparable, while the duration of action was drug-specific.

The influence of a continuous rate infusion of dexmedetomidine on the nociceptive withdrawal reflex and temporal summation during isoflurane anaesthesia in dogs

Objective To examine the influence of a low dose dexmedetomidine infusion on the nociceptive withdrawal reflex and temporal summation in dogs during isoflurane anaesthesia. Study design Prospective experimental blinded cross-over study. Animals Eight healthy mixed breed dogs, body weight Mean +/- SD 26.5 +/- 8.4 kg and age 25 +/- 16 months. Methods Anaesthesia was induced with propofol and maintained with isoflurane (Fe'ISO 1.3%) delivered in oxygen and air. After stabilization, baseline recordings (time 0) were obtained, then a dexmedetomidine bolus (1 mug kg(-1) IV) followed by a continuous rate infusion (1 mug kg(-1) hour(-1) ) or saline placebo were administered. At times 10, 30 and 60 minutes after the initial bolus, electrical stimulations of increasing intensity were applied over the lateral plantar digital nerve, and administered both as single and as repeated stimuli. The resulting reflex responses were recorded using electromyography. Data were analysed using a multivariable linear regression model and a Kruskal Wallis test for single stimulation data, and repeated measures anova and paired t-test for repeated stimulation data. Results The AUC for the stimulus-response curves after single stimulation were similar for both treatments at time 0. At times 10, 30 and 60 the AUCs for the stimulus-response curves were significantly lower with dexmedetomidine treatment than with placebo. Temporal summation was evident in both treatments at times 0, 10, 30 and 60 starting from a stimulation intensity of 10 mA. The magnitude of temporal summation was smaller in dexmedetomidine than in placebo treated dogs at time 10, 30 and 60, but not at time 0. Conclusions During isoflurane anaesthesia, low dose dexmedetomidine suppresses the nociceptive reflex responses after single and repeated electrical stimulation. Clinical relevance This experimental study confirms previous reports on its peri-operative efficacy under clinical conditions, and further indicates that dexmedetomidine might reduce the risk of post-operative chronic pain development.

Weighted Majoritarian Rules for the Location of Multiple Public Facilities

We consider collective decision problems given by a profile of single-peaked preferences defined over the real line and a set of pure public facilities to be located on the line. In this context, Bochet and Gordon (2012) provide a large class of priority rules based on efficiency, object-population monotonicity and sovereignty. Each such rule is described by a fixed priority ordering among interest groups. We show that any priority rule which treats agents symmetrically — anonymity — respects some form of coherence across collective decision problems — reinforcement — and only depends on peak information — peakonly — is a weighted majoritarian rule. Each such rule defines priorities based on the relative size of the interest groups and specific weights attached to locations. We give an explicit account of the richness of this class of rules.

Modulus and Poincaré Inequalities on Non-Self-Similar Sierpiński Carpets

A carpet is a metric space homeomorphic to the Sierpiński carpet. We characterize, within a certain class of examples, non-self-similar carpets supporting curve families of nontrivial modulus and supporting Poincaré inequalities. Our results yield new examples of compact doubling metric measure spaces supporting Poincaré inequalities: these examples have no manifold points, yet embed isometrically as subsets of Euclidean space.