Imaging of Colorectal Liver Metastasis.

Colorectal cancer (CRC) is one of the most common cancers in the world. The most important determinant of survival and prognosis is the stage and presence of metastasis. The liver is the most common location for CRC metastasis. The only curative treatment for CRC liver metastasis (CRLM) is resection; however, many patients are ineligible for surgical resection of CRLM. Locoregional treatments such as ablation and intra-arterial therapy are also available for patients with CRLM. Assessment of response after chemotherapy is challenging due to anatomical and functional changes. Antiangiogenic agents such as bevacizumab that are used in the treatment of CRLM may show atypical patterns of response on imaging. It is vital to distinguish patterns of response in addition to toxicities to various treatments. Imaging plays a critical role in evaluating the characteristics of CRLM and the approach to treatment. CT is the modality of choice in the diagnosis and management of CRLM. MRI is best used for indeterminate lesions and to assess response to intra-arterial therapy. PET-CT is often utilized to detect extrahepatic metastasis. State-of-the-art imaging is critical to characterize patterns of response to various treatments. We herein review the imaging characteristics of CRLM with an emphasis on imaging changes following the most common CRLM treatments.

Validation of a coupled electromagnetic and thermal model for estimating temperatures during magnetic nanoparticle hyperthermia.

PURPOSE: Alternating magnetic field (AMF) tissue interaction models are generally not validated. Our aim was to develop and validate a coupled electromagnetic and thermal model for estimating temperatures in large organs during magnetic nanoparticle hyperthermia (MNH). MATERIALS AND METHODS: Coupled finite element electromagnetic and thermal model validation was performed by comparing the results to experimental data obtained from temperatures measured in homogeneous agar gel phantoms exposed to an AMF at fixed frequency (155 ± 10 kHz). The validated model was applied to a three-dimensional (3D) rabbit liver built from computed tomography (CT) images to investigate the contribution of nanoparticle heating and nonspecific eddy current heating as a function of AMF amplitude. RESULTS: Computed temperatures from the model were in excellent agreement with temperatures calculated using the analytical method (error < 1%) and temperatures measured in phantoms (maximum absolute error <2% at each probe location). The 3D rabbit liver model for a fixed concentration of 5 mg Fe/cm3 of tumor revealed a maximum temperature ∼44 °C in tumor and ∼40 °C in liver at AMF amplitude of ∼12 kA/m (peak). CONCLUSION: A validated coupled electromagnetic and thermal model was developed to estimate temperatures due to eddy current heating in homogeneous tissue phantoms. The validated model was successfully used to analyze temperature distribution in complex rabbit liver tumor geometry during MNH. In future, model validation should be extended to heterogeneous tissue phantoms, and include heat sink effects from major blood vessels.

Imaging neuroendocrine tumors: Characterizing the spectrum of radiographic findings.

Neuroendocrine tumors (NET) are a group of neoplasms with neuroendocrine differentiation affecting a wide range of organs. Functional NETs present with symptoms due to the particular hormone produced. Functional NETs are usually small at diagnosis and therefore can be challenging to diagnose. In contrast, non-functioning NETs are generally larger and present with mass effect. Imaging plays an indispensable role in diagnosis, staging and management of patients with NETs. The optimal modality and technique for imaging of NETs depend on the location of primary and metastatic lesions. Regardless of the imaging modality, dynamic contrast-enhanced imaging is essential for evaluation of NETs. In general, CT scan is typically the primary imaging modality for evaluating NETs. MRI is used as a complementary modality, being superior to other modalities to assess liver metastasis. Nuclear medicine imaging is also widely used in NET assessment.

Theranostic application of lipiodol for transarterial chemoembolization in a VX2 rabbit liver tumor model.

The goal of this study was to investigate the role of Lipiodol as a tumor-specific imaging biomarker to determine therapeutic efficacy of cTACE and investigate its inter-dependency with tumor perfusion using radiological-pathological correlation in an animal model of liver cancer. METHODS: A total of N=36 rabbits were implanted in the left lobe of the liver with VX2 tumors, treated with cTACE using doxorubicin suspended in Lipiodol, and randomly sacrificed at 24 h, 7 days, or 20 days post-TACE. Unenhanced and contrast-enhanced CT scans including a perfusion protocol were obtained before cTACE and immediately before sacrifice. Tumor vascularity and Lipiodol deposition within tumors and hepatic tissue (non-target deposits) were quantified using 3D quantitative assessment tools and measurements of arterial flow, portal flow, and perfusion index (PI). After sacrifice histologic staining, including hematoxylin and eosin (H&E), CD31, and Oil Red O (ORO) were performed on tumor and liver samples to evaluate necrosis, microvascular density (MVD), and Lipiodol retention over time. Transmission electron microscopy (TEM) was performed to assess Lipiodol deposition and clearance over time. RESULTS: All cTACE procedures were carried out successfully except for one, which was excluded from further analysis. Twenty-four hours post-TACE, tumor PI (p=0.04) was significantly decreased, which was maintained at 7 days (p=0.003), but not at 20 days (p=0.4). A strong correlation (R2 = 0.894) was found between the volume of enhancing tumor tissue at baseline and Lipiodol-positive tumor volume post-TACE. Both ORO and TEM showed deposition of Lipiodol across all imaging time points within the VX2 tumors. However, gradual and ultimately near-complete Lipiodol washout was observed over time in the non-tumoral liver. MVD decreased between 24 h and 7 days post-TACE, and then increased 20 days post-TACE (both p<0.01). CONCLUSIONS: Our data provide radiology-pathology evidence for the function of Lipiodol as a theranostic, tumor-specific drug delivery agent because it is both imageable and tumor-seeking, whereby it is preferentially taken up and retained by tumor cells. Those tumor-specific functions also enable Lipiodol to act as an imaging biomarker for the therapeutic efficacy of cTACE. Together with volumetric quantification of tumor vascularization on CT, Lipiodol could be used as a predictor of a patient's response to cTACE and contribute to the therapeutic management of patients with liver cancer.

Impact of DAT-SPECT on Management of Patients Suspected of Parkinsonism.

OBJECTIVE: To evaluate the value of I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT-SPECT) to change management strategies of patients suspected of parkinsonism. METHOD: This was an institutional review board-approved, retrospective study. DAT-SPECT scans ordered by movement disorder specialist and neurologists from 2011-2014 were reviewed. Clinical data and radiological reports of 173 patients suspected of parkinsonism were reviewed. The DAT-SPECT scan results were correlated with clinical assessment and treatment changes. RESULTS: A total of 173 patients (104 male and 69 female subjects; age, 64.4 ± 12.6 years) suspected of parkinsonism were included. Median duration of symptoms was 36 months (range, 1-480 months). Scans were most often requested when there was diagnostic uncertainty in clinical features (59.6%, 103/173) or to differentiate one other disease from parkinsonism such as Parkinson disease (PD) versus essential tremor (23.7%, 41/173), PD versus drug-induced parkinsonism (8.7%, 15/173), or PD versus psychogenic (6.4%, 11/173) or vascular (1.7%, 3/173) disorders. Patients were classified, according to the DAT-SPECT scanning results, as those with abnormal DAT-SPECT findings (59%, 102/173) and those with normal DAT-SPECT findings (41%, 71/173). In patients with normal DAT-SPECT findings, follow-up management data were available in 76.1% (54/71). The management changed in 39.4% (28/54) after DAT scan with starting a new appropriate medications or supportive therapy in 4.2% (3/28), withholding inappropriate dopaminergic treatment in 11.3% (8/28), or continuing observation in 23.9% (17/28). In patients with abnormal DAT-SPECT findings, follow-up management data were available in 78.4% (80/102). There was change in management of 37.3% (38/80), a new PD treatment was started in 89.5% (34/38). The dose of medication was adjusted in 5.3% (2/38), although the original treatment was not changed. Parkinson disease treatment was stopped in 2.6% (1/38) and discontinued in 2.6% (1/38) based on clinical decision of neurologists despite abnormal DAT-SPECT findings. CONCLUSIONS: DAT-SPECT findings impacted treatment decisions in 44.7% of patients suspected of Parkinsonism.

Papillary Breast Lesions: Association with Malignancy and Upgrade Rates on Surgical Excision.

Intraductal papilloma falls under the category of benign breast mass. However, recent studies show that it can harbor occult carcinoma. The management of benign intraductal papilloma remains controversial because of its nonspecific radiologic and histological findings, as well as its association with surrounding malignant pathology. The purpose of this study is to investigate upgrade rates of a benign intraductal papilloma on surgical excision and the need for surgical excision of papillary lesions diagnosed at core needle biopsy. A retrospective review of a single institution's pathology database between 2011 and 2015 identified 43 core biopsies with benign papilloma. We followed the upgrade rates of these lesions on surgical excision. There were 90 biopsies with the diagnosis of benign intraductal papilloma. The average age was 55.2 (range from 24-87 years old). Forty-three had benign intraductal papilloma; 28 of the 43 core biopsies had surgical excision. Two (7.1%) had an upgrade from benign intraductal papilloma to intraductal papilloma with atypia. One (3.6%) had an upgrade to ductal carcinoma in situ. None had invasive cancer. Surgical findings were in agreement with core biopsies in 25 (89.3%) of 28 cases (κ = 0.80, P < 0.0001). Core biopsies have a statistically significant correlation with pathologies on surgical excision in detecting atypia in breast lesion as demonstrated by κ = 0.80. However, the study shows benign intraductal papillomas on core biopsy have an upgrade rate of 10.7 per cent after undergoing surgical excision. As such, we recommend a more aggressive approach including surgical excision of all benign intraductal papillary lesions.

Preclinical Benefit of Hypoxia-Activated Intra-arterial Therapy with Evofosfamide in Liver Cancer.

PURPOSE: To evaluate safety and characterize anticancer efficacy of hepatic hypoxia-activated intra-arterial therapy (HAIAT) with evofosfamide in a rabbit model. EXPERIMENTAL DESIGN: VX2-tumor-bearing rabbits were assigned to 4 intra-arterial therapy (IAT) groups (n = 7/group): (i) saline (control); (ii) evofosfamide (Evo); (iii) doxorubicin-lipiodol emulsion followed by embolization with 100-300 µm beads (conventional, cTACE); or (iv) cTACE and evofosfamide (cTACE + Evo). Blood samples were collected pre-IAT and 1, 2, 7, and 14 days post-IAT. A semiquantitative scoring system assessed hepatocellular damage. Tumor volumes were segmented on multidetector CT (baseline, 7/14 days post-IAT). Pathologic tumor necrosis was quantified using manual segmentation on whole-slide images. Hypoxic fraction (HF) and compartment (HC) were determined by pimonidazole staining. Tumor DNA damage, apoptosis, cell proliferation, endogenous hypoxia, and metabolism were quantified (γ-H2AX, Annexin V, caspase-3, Ki-67, HIF1α, VEGF, GAPDH, MCT4, and LDH). RESULTS: cTACE + Evo showed a similar profile of liver enzymes elevation and pathologic scores compared with cTACE. Neither hematologic nor renal toxicity were observed. Animals treated with cTACE + Evo demonstrated smaller tumor volumes, lower tumor growth rates, and higher necrotic fractions compared with cTACE. cTACE + Evo resulted in a marked reduction in the HF and HC. Correlation was observed between decreases in HF or HC and tumor necrosis. cTACE + Evo promoted antitumor effects as evidenced by increased expression of γ-H2AX, apoptotic biomarkers, and decreased cell proliferation. Increased HIF1α/VEGF expression and tumor glycolysis supported HAIAT. CONCLUSIONS: HAIAT achieved a promising step towards the locoregional targeting of tumor hypoxia. The favorable toxicity profile and enhanced anticancer effects of evofosfamide in combination with cTACE pave the way towards clinical trials in patients with liver cancer. Clin Cancer Res; 23(2); 536-48. ©2016 AACR.

Potential Role of Cardiovascular Imaging in Improving Cardiovascular Outcome in Coronary Artery Disease.

BACKGROUND: There is increasing interest in cardiovascular imaging modalities in the detection of subclinical and clinically-manifested coronary artery disease (CAD) to improve cardiovascular outcome in these patients. METHODS: SPECT/CT and PET/CT can be applied for the assessment of myocardial perfusion and myocardial blood flow (MBF) quantification in CAD detection and characterization, while CT is predominantly used to identify coronary plaque burden and epicardial narrowing. In addition, PET/CT plays an increasing role in the detection of the "vulnerable" plaque in the epicardial artery. RESULTS: Imaging of myocardial perfusion with SPECT, SPECT/CT and PET/CT is a mainstay in clinical practice for the identification of flow-limiting epicardial lesions and risk stratification of patients with suspected or known CAD. In this direction, the concurrent ability of PET/CT to determine regional myocardial blood flow (MBF) in ml/g/min at rest and during pharmacologically- induced hyperemic flows allows the calculation of the myocardial flow reserve (MFR) that may unravel reductions in coronary vasodilator capacity, as functional precursor of the CAD process, monitor its response to preventive medical intervention, yield important prognostic information in subclinical - and clinically-manifested CAD, and contributes to identify the flow-limiting effect of single lesions in multivessel CAD. Adding noncontrast computed-tomography (CT) measurements of coronary artery calcifications has further improved the reclassification of cardiovascular risk in asymptomatic individuals with intermediate probability of the presence of CAD. With contrast CT, the non-invasive visualization of coronary vessels, CAD-related plaque burden and stenosis has become feasible. Yet, a definite identification of the "vulnerable plaque" is still a matter of ongoing research. PET/CT in conjunction with various positron-emitting radiotracer yields promise in the detection of the "vulnerable plaque," that, however, needs further clinical evaluation in CAD patients. CONCLUSION: Multimodality imaging in cardiovascular disease is likely to further advances and refine the identification and characterization of cardiovascular pathology in the near future.

Utilizing the micron sized non-thermal atmospheric pressure plasma inside the animal body for the tumor treatment application.

This study aimed to evaluate the effects of micron sized non-thermal atmospheric pressure plasma inside the animal body on breast cancer tumor. The µ-plasma jet consists of micron sized hollow tube in which pure helium gas is ionized by high voltage (4 kV) and high frequency (6 kHz). The efficiency of the plasma treatment in killing cancer cells was first investigated by cell viability measurements of treated 4T1 cells using flow cytometry and cell cycle analysis. For exploration of the in vivo effects of the plasma treatment, the BALB/c mice inoculated by 4T1 cell lines were exposed subcutaneously to plasma for 3 minutes. In addition, H&E staining, TUNEL and Western blotting assays were performed in order to observed the effects of the non-thermal plasma on the tumor cells. The results showed that the efficiency of the plasma in suppression of the tumor growth is comparable to that of a typical chemotherapy drug. Moreover, the results indicated that the plasma induces apoptosis in the tumor tissue and increases the ratio of the apoptotic to anti-apoptotic protein expression. We believe that these findings presented herein may extend our knowledge of the mechanisms by which the plasma exerts its promising anti-cancer effects.

18F-FDG PET/CT and Melanoma: Value of Fourth and Subsequent Posttherapy Follow-up Scans for Patient Management.

PURPOSE: We aimed to evaluate the added value of performing fourth and subsequent follow-up F-FDG-PET/CT scans to clinical assessment and impact on the patient's management in patients with melanoma. METHODS: This was a retrospective study of 232 biopsy-proven melanoma patients who underwent F-FDG-PET/CT scans. Of these, 71 patients had 4 or more follow-up F-FDG-PET/CT scans after completion of primary treatment, with a total of 246 fourth or subsequent follow-up PET/CT scans. The added value of each follow-up PET/CT scan to the patient's clinical assessment and treatment management was established. Kaplan-Meier plots with a Mantel-Cox log-rank test were used to establish the patient's overall survival. RESULTS: Of the 246 fourth and subsequent follow-up PET/CT scans, 61% (150/246) were negative for malignancy, and 39.0% (96/246) were positive for recurrence/metastases. FDG-PET/CT was helpful in identifying malignancy in 6.5% of the scans performed without prior clinical suspicion, which ruled out malignancy in 28.5% of the scans obtained with prior clinical signs suggestive of recurrence or for secondary therapy assessment. The PET/CT scan resulted in change of the patient's management in approximately 16.7% (41/246) of the scans. Change in management was significantly greater in patients whose scans were done with prior clinical signs suggestive of malignancy, or for therapy assessment than without prior clinical suspicion (29.3% vs 4.1%; P < 0.0001). Statistically significant difference was seen in the overall survival between patients with at least 1 positive and all negative fourth and subsequent follow-up PET/CT scans at patient level (P = 0.001). CONCLUSIONS: The fourth and subsequent F-FDG-PET/CT scans obtained after completion of primary treatment added value to clinical assessment in patients with melanoma. Patients with clinical signs suggestive of recurrence or metastases or being monitored for treatment response are more likely to benefit from the fourth or subsequent FDG PET/CT than those without prior clinical suspicion.

Image-guided thermal therapy with a dual-contrast magnetic nanoparticle formulation: A feasibility study.

PURPOSE/OBJECTIVE: The aim of this study was to develop and investigate the properties of a magnetic iron oxide nanoparticle-ethiodised oil formulation for image-guided thermal therapy of liver cancer. MATERIALS AND METHODS: The formulation comprises bionised nano-ferrite (BNF) nanoparticles suspended in ethiodised oil, emulsified with polysorbate 20 (BNF-lip). Nanoparticle size was measured via photon correlation spectroscopy and transmission electron microscopy. In vivo thermal therapy capability was tested in two groups of male Foxn1(nu) mice bearing subcutaneous HepG2 xenograft tumours. Group I (n = 12) was used to screen conditions for group II (n = 48). In group II, mice received one of BNF-lip (n = 18), BNF alone (n = 16), or PBS (n = 14), followed by alternating magnetic field (AMF) hyperthermia, with either varied duration (15 or 20 min) or amplitude (0, 16, 20, or 24 kA/m). Image-guided fluoroscopic intra-arterial injection of BNF-lip was tested in New Zealand white rabbits (n = 10), bearing liver VX2 tumours. The animals were subsequently imaged with CT and 3 T MRI, up to 7 days post-injection. The tumours were histopathologically evaluated for distribution of BNF-lip. RESULTS: The BNF showed larger aggregate diameters when suspended in BNF-lip, compared to clear solution. The BNF-lip formulation produced maximum tumour temperatures with AMF >20 kA/m and showed positive X-ray visibility and substantial shortening of T1 and T2 relaxation time, with sustained intratumoural retention up to 7 days post-injection. On pathology, intratumoural BNF-lip distribution correlated well with CT imaging of intratumoural BNF-lip distribution. CONCLUSION: The BNF-lip formulation has favourable thermal and dual imaging capabilities for image-guided thermal therapy of liver cancer, suggesting further exploration for clinical applications.

A Novel Inherently Radiopaque Bead for Transarterial Embolization to Treat Liver Cancer - A Pre-clinical Study.

PURPOSE: Embolotherapy using microshperes is currently performed with soluble contrast to aid in visualization. However, administered payload visibility dimishes soon after delivery due to soluble contrast washout, leaving the radiolucent bead's location unknown. The objective of our study was to characterize inherently radiopaque beads (RO Beads) in terms of physicomechanical properties, deliverability and imaging visibility in a rabbit VX2 liver tumor model. MATERIALS AND METHODS: RO Beads, which are based on LC Bead® platform, were compared to LC Bead. Bead size (light microscopy), equilibrium water content (EWC), density, X-ray attenuation and iodine distribution (micro-CT), suspension (settling times), deliverability and in vitro penetration were investigated. Fifteen rabbits were embolized with either LC Bead or RO Beads + soluble contrast (iodixanol-320), or RO Beads+dextrose. Appearance was evaluated with fluoroscopy, X-ray single shot, cone-beam CT (CBCT). RESULTS: Both bead types had a similar size distribution. RO Beads had lower EWC (60-72%) and higher density (1.21-1.36 g/cc) with a homogeneous iodine distribution within the bead's interior. RO Beads suspension time was shorter than LC Bead, with durable suspension (>5 min) in 100% iodixanol. RO Beads ≤300 µm were deliverable through a 2.3-Fr microcatheter. Both bead types showed similar penetration. Soluble contrast could identify target and non-target embolization on fluoroscopy during administration. However, the imaging appearance vanished quickly for LC Bead as contrast washed-out. RO Beads+contrast significantly increased visibility on X-ray single shot compared to LC Bead+contrast in target and non-target arteries (P=0.0043). Similarly, RO beads demonstrated better visibility on CBCT in target arteries (P=0.0238) with a trend in non-target arteries (P=0.0519). RO Beads+dextrose were not sufficiently visible to monitor embolization using fluoroscopy. CONCLUSION: RO Beads provide better conspicuity to determine target and non-target embolization compared to LC Bead which may improve intra-procedural monitoring and post-procedural evaluation of transarterial embolization.

Evaluation of 70-150-µm doxorubicin-eluting beads for transcatheter arterial chemoembolization in the rabbit liver VX2 tumour model.

AIM: To evaluate the pharmacokinetic profile (PK) and embolization effect of 70-150-µm doxorubicin eluting beads (DEBs) following intra-arterial injection (i.a.) in the rabbit liver VX2 tumour model. MATERIALS AND METHODS: In this ACUC-approved study, 25 white New Zealand rabbits were randomly assigned into a small DEB group (SDB, n = 7, 70-150-µm DEBs), large DEB group (LDB, n = 7, 100-300-µm DEBs), untreated controls (n = 7), and doxorubicin controls (n = 4, without tumour, received i.a. 12.5 mg doxorubicin). Plasma PK was assessed up to 180 min post-injection. Drug tissue and liver enzyme levels, radiologic tumor response and histopathologic tumour necrosis were assessed at 7 days. RESULTS: Mean tumour doxorubicin concentrations were 922.83 nM (SD = 722.05) and 361.48 nM (SD = 473.23) for the SDB and LDB, respectively (p = 0.005). There was no statistically significant difference in tumour doxorubicinol, plasma doxorubicin and doxorubicinol PK values. More beads were observed in the SDB tumours (p = 0.01). Liver enzymes increased and gradually declined over the observation period, with significantly higher values in the SDB. CONCLUSION: In this preclinical study, plasma PK of i.a.-injected 70-150-µm DEBs was not different than that of 100-300-µm DEBs. More beads and higher tissue doxorubicin levels were observed in the SDB tumours. KEY POINTS: • Small and large doxorubicin-eluting beads show similar plasma pharmacokinetic profiles. • Higher tissue doxorubicin levels were observed in the small bead group. • Liver enzymes were overall significantly higher in the small bead group.

The role of PET/CT in the management of cervical cancer.

OBJECTIVE. Cervical cancer is the second most common malignancy in women worldwide and the third most common cause of cancer mortality in the United States. The aim of this article is to describe cervical cancer and outline the value of (18)F-FDG PET/CT in the management of cervical malignancy. CONCLUSION. The value of PET/CT has been found in staging and treatment strategy for cervical cancer. FDG PET/CT facilitates decision-making and radiation treatment planning and provides important information about treatment response, disease recurrence, and long-term survival.

Rate dependent left bundle branch block: the pattern of myocardial perfusion SPECT.

We report myocardial perfusion SPECT pattern in four subsequent patients with rate dependent left bundle branch block (LBBB). Three females and one male (aged 48, 51, 63 and 67 years) were studied. None of the patients had history of typical chest pain and all suffered from atypical chest pain or dyspnea on exertion. All patients were tested for baseline and serial heart rate, blood pressure, and electrocardiogram recordings. The exercise treadmill tests (ETT) were carried out under the strict supervision of a cardiologist, a nuclear medicine physician and close availability of an expert cardio-pulmonary resuscitation team and cardiac care unit within just few seconds. Maximal stress test (at least 85% of calculated heart rate, following development of LBBB) was achieved in all four patients according to standard Bruce protocol. No adverse cardiac events were noted and all ETT stress protocols terminated completely and safely. Myocardial perfusion SPECT imaging showed no evidence of reversible perfusion defects. The only patient with past history of exercise induced LBBB showed nonreversible perfusion defects in the septal and anteroseptal regions and mild LV cavity dilatation. The limited number of patients enrolled in our study does not allow us to draw a definite conclusion. Despite the presence of false-positive defects in myocardial perfusion SPECT in patients with sustained LBBB, such a finding is not a consistent finding in patients with rate dependent or exercised-induced LBBB, unlike that which we expected to see. Maybe it is possible to continue ETT for those patients undergoing myocardial perfusion scintigraphy and developing rate dependent LBBB.

Association between puberty and weight, height and body mass index in a developing community.

OBJECTIVE: To evaluate the epidemiology of pubertal development of girls in a developing community. METHODS: The cross-sectional study was undertaken in July 2005, on 788 healthy 7-16 years old girls in Gorgan, the most populous city of Golestan province in northern Iran. Physical examination, was performed and height, weight and body mass index were noted. Pubertal stages were assessed by clinical examination according to the methods of Marshall and Tanner, while the mean menarcheal age was calculated by using the status quo method. The data was treated with analysis of variance Pearson's linear regression and SPSS version 16.0. RESULTS: The mean age, weight, height and BMI +/- standard deviation of the studied girls were 10.32 +/- 2.48 years, 35.07 +/- 11.30 kg, 140.11 +/- 14.62 cm, and 17.34 +/- 3.55 kg/m2 respectively. Menarche had occurred with the mean menarcheal age being 12.15 +/- 1.11 years. The mean age at the onset of breast development was 10.55 +/- 1.57 years. There was no significant association between mean height, weight and BMI and the menarcheal age and pubertal stage. CONCLUSION: Based on the epidemiology of pubertal development of girls in the study, there seems to be a case for creating particular guidelines for pubertal development assessment for each type of society in addition to the standard international guidelines in this regard.

Renal axis deviation in urinary tract abnormalities of children: the role of renal scintigraphy.

BACKGROUND: Urinary tract pathologies are common in children. Previous reports suggested a relationship between some renal pathologies and renal anatomic variations. This study evaluates the effect of different urinary tract abnormalities on scintigraphic renal long axis. METHODS: Children referred to our nuclear medicine department for Tc-99m dimercaptosuccinic acid and/or Tc-99m N,N-ethylenedicysteine renal scintigraphies were entered consecutively. Presence of single, ectopic, or fused kidneys, extrarenal pathologies altering renal long axis, and history of renal surgery or advanced renal disease were used as exclusion criteria. If indicated, patients were assessed for vesicoureteral reflux (VUR). Long renal axis of each kidney was drawn with a line passing through the kidney's upper and lower poles using posterior image. The angle between this axis and patient's longitudinal body axis was defined as "renal angle." After defining age-groups, "age-corrected renal angle" was calculated. RESULTS: A total of 311 cases (622 kidney units) entered the study (183 females, 128 males). Mean age was 41.8 months. Mean "renal angle" was 11.7, 11.9, 14.1, 17.6, 28.5, 16.7, and 19.2 degrees in normal, mild, moderate, and severe VUR, high-grade ureteropelvic junction (UPJ) obstruction, nonobstructive pelvic dilatation, and ureterovesical junction obstruction, respectively (P = 0.000). Applying receiver operating characteristic analysis and using ultrasonography as the gold standard, renal angle deviation of 13.75 degrees led to the sensitivity of 74.6% and specificity of 70.7% to detect pyelocalyceal system dilatation. Using a "renal angle" cutoff value of 18.7 degrees, 85% sensitivity and 85% specificity were achieved for the diagnosis of high-grade UPJ obstruction. Using "age-corrected renal angle," a cutoff value of 3.9 degrees was consistent with 60% sensitivity and 73% specificity for the diagnosis of severe VUR. CONCLUSION: Considerable renal axis deviation is noted in patients with UPJ obstruction and severe VUR in children. Measurement of "renal angle" provides indirect but useful clues to the presence of urinary tract pathologies. Renal scintigraphy is a useful tool for drawing renal axis and measuring "renal angle," potentially making it useful for prediction of urinary tract system abnormalities.

Appropriateness of referrals for single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in a developing community: a comparison between 2005 and 2009 versions of ACCF/ASNC appropriateness criteria.

INTRODUCTION: Appropriateness of referrals for myocardial perfusion imaging (MPI) in developing countries has not been extensively studied. Our study was conducted to describe the ordering practices of physicians and appropriateness of MPI referrals in Iran. METHOD: We prospectively applied 2005 and 2009 versions of the Appropriateness Use Criteria published by the American College of Cardiology Foundation (ACCF) and the American Society of Nuclear Cardiology (ASNC) to 291 consecutive patients (age 55.3 ± 10.3 years) who underwent SPECT-MPI. For this purpose, we convened a panel, consisting of two academic cardiologists, one academic clinician in internal medicine, and one academic clinician in nuclear medicine. The panelists were invited for a face-to-face meeting to judge appropriateness of SPECT-MPI and independently assign a specific indication (scenario), whenever possible, for each case in accordance with ACCF/ASNC appropriateness scenarios. RESULTS: Based on the 2005 ACCF/ASNC criteria, SPECT-MPI studies were judged appropriate for 211 (72.5%), uncertain for 36 (12.4%), inappropriate for 32 (11.0%), and unclassifiable for 12 (4.1%) referrals. The same figures based on the 2009 version were 219 (75.3%), 15 (5.2%), 49 (16.8%), and 8 (2.7%) patients, respectively. Overall agreement between the 2005 and 2009 versions was good (κ 0.63). Lack of chest pain and age below 60 years were significant indicators increasing the likelihood of inappropriate referrals by 2.9-3.4 fold. Absence of diabetes mellitus and hypertension, a normal lipid profile, lack of a past history of myocardial infarction or cardiovascular interventions (CABGs or PCI), as well as lack of application and exercise ECG stress test as the gate keeper (keeping abnormal ETT or inability of the patient to perform exercise as the appropriate indication for SPECT-MPI referral) were significant indicators, decreasing the odds of appropriate referrals. Generally a higher percentage of referrals with inappropriate indications had normal MPI. CONCLUSION: Our study provides an evidence for the fact that SPECT-MPI ordering practices in our developing community largely parallel the ACCF/ASNC recommendations. The implementation of appropriateness criteria is feasible in clinical settings and might provide an alternative to utilization management.