Abbreviated breast magnetic resonance imaging (MRI) or digital breast tomosynthesis for breast cancer detection in dense breasts? A retrospective preliminary study with comparable results.

AIM: To compare the diagnostic performance of abbreviated breast magnetic resonance (AB-MR) imaging (MRI) and digital breast tomosynthesis (DBT) for breast cancer detection in Malaysian women with dense breasts, using histopathology as the reference standard. MATERIALS AND METHODS: This was a single-centre cross-sectional study of 115 women with American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BIRADS) breast density C and D on DBT with breast lesions who underwent AB-MR from June 2018 to December 2021. AB-MR was performed on a 3 T MRI system with an imaging protocol consisting of three sequences: axial T1 fat-saturated unenhanced; axial first contrast-enhanced; and subtracted first contrast-enhanced with maximum intensity projection (MIP). DBT and AB-MR images were evaluated by two radiologists blinded to the histopathology and patient outcomes. Diagnostic accuracy (sensitivity, specificity, positive predictive value [PPV] and negative predictive value [NPV]) was assessed. RESULT: Of the 115 women, the mean age was 50.6 years. There were 48 (41.7%) Malay, 54 (47%) Chinese, and 12 (10.4%) Indian women. The majority (n=87, 75.7%) were from the diagnostic population. Sixty-one (53.1%) were premenopausal and 54 (46.9%) postmenopausal. Seventy-eight (72.4%) had an increased risk of developing breast cancer. Ninety-one (79.1%) women had density C and 24 (20.9%) had density D. There were 164 histopathology-proven lesions; 69 (42.1%) were malignant and 95 (57.9%) were benign. There were 62.8% (n=103/164) lesions detected at DBT. All the malignant lesions 100% (n=69) and 35.7% (n=34) of benign lesions were detected. Of the 61 lesions that were not detected, 46 (75.4%) were in density C, and 15 (24.6%) were in density D. The sensitivity, specificity, PPV, and NPV for DBT were 98.5%, 34.6%, 66.3%, and 94.7%, respectively. There were 65.2% (n=107/164) lesions detected on AB-MR, with 98.6% (n=68) malignant and 41.1% (39) benign lesions detected. The sensitivity, specificity, PPV, and NPV for AB-MR were 98.5%, 43.9%, 67.2%, and 96.2%, respectively. One malignant lesion (0.6%), which was a low-grade ductal carcinoma in-situ (DCIS), was missed on AB-MR. CONCLUSION: The present findings suggest that both DBT and AB-MR have comparable effectiveness as an imaging method for detecting breast cancer and have high NPV for low-risk lesions in women with dense breasts.

The effectiveness of an ultrafast breast MRI protocol in the differentiation of benign and malignant breast lesions.

AIM: To evaluate the effectiveness of an ultrafast breast magnetic resonance imaging (MRI) protocol in differentiating benign and malignant breast lesions. MATERIALS AND METHODS: Fifty-four patients with Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 lesions were recruited between July 2020 to May 2021. A standard breast MRI was performed with the inclusion of the ultrafast protocol between the unenhanced sequence and the first contrast-enhanced sequence. Three radiologists performed image interpretation in consensus. Ultrafast kinetic parameters analysed included the maximum slope (MS), time to enhancement (TTE), and arteriovenous index (AVI). These parameters were compared using receiver operating characteristics with p-values of <0.05 considered to indicate statistical significance. RESULTS: Eighty-three histopathological proven lesions from 54 patients (mean age 53.87 years, SD 12.34, range 26-78 years) were analysed. Forty-one per cent (n=34) were benign and 59% (n=49) were malignant. All malignant and 38.2% (n=13) benign lesions were visualised on the ultrafast protocol. Of the malignant lesions, 77.6% (n=53) were invasive ductal carcinoma (IDC) and 18.4% (n=9) were ductal carcinoma in situ (DCIS). The MS for malignant lesions (13.27%/s) were significantly larger than for benign (5.45%/s; p<0.0001). No significant differences were seen for TTE and AVI. The area under the ROC curve (AUC) for the MS, TTE, and AVI were 0.836, 0.647, and 0.684, respectively. Different types of invasive carcinoma had similar MS and TTE. The MS of high-grade DCIS was also similar to that of IDC. Lower MS values were observed for low-grade (5.3%/s) compared to high-grade DCIS (14.8%/s) but the results were not significant statistically. CONCLUSION: The ultrafast protocol showed potential to discriminate between malignant and benign breast lesions with high accuracy using MS.

Differential Effects of Clinically Relevant N- versus C-Terminal Truncating CDKN1A Mutations on Cisplatin Sensitivity in Bladder Cancer.

Muscle-invasive bladder cancer (MIBC) frequently harbors mutations in the CDKN1A gene, which encodes the tumor suppressor protein p21, with the majority of alterations truncating the peptide. The effect of these mutations is poorly understood. We hypothesized that after DNA-damaging events, cells deficient in p21 would be unable to halt the cell cycle and efficiently repair DNA damage, thus proceeding down the apoptotic pathway. We used synthetic CRISPR guide RNAs to ablate the whole peptide (sg12, targeting the 12th amino acid) or the C-terminal proliferating cell nuclear antigen (PCNA)-binding domain (sg109) to mimic different p21-truncating mutations compared with a negative control (sgGFP) in bladder cancer cell lines. Loss of detectable p21 and a stable truncated p21 peptide were identified in sg12 and sg109 single-cell clones, respectively. We found that p21-deficient cells (sg12) were sensitized to cisplatin, while cells harboring distally truncated p21 (sg12 clones) demonstrated enhanced cisplatin resistance. p21-deficient sg12 clones demonstrated less repair of DNA-platinum adducts and increased γ-H2AX foci after cisplatin exposure, suggesting there was persistent DNA damage after p21 loss. p21-deficient sg12 clones were also unable to prevent the activation of CDK1 after DNA damage, and therefore, continued through the cell cycle, resulting in replication fork collapse, potentially explaining the observed cisplatin sensitization. sg109 clones were neither unable to sequester PCNA nor localize p21 to the nucleus after DNA damage, potentially explaining the chemoresistant phenotype. Our findings suggest that different CDKN1A truncations have different and perhaps disparate biology, and that there may be a duality of effect on cisplatin sensitivity depending on mutation context. IMPLICATIONS: Some truncating CDKN1A mutations generate a retained peptide that may have neomorphic functions and affect cisplatin sensitivity in patients with bladder cancer.

Correlation and accuracy of contrast-enhanced computed tomography in assessing depth of invasion of oral tongue carcinoma.

The aim of this study was to evaluate the correlation and accuracy of depth of invasion (DOI) measurement from preoperative contrast-enhanced computed tomography (CECT) scans in comparison to histopathological examination (HPE) in oral tongue squamous cell carcinoma (OTSCC). Preoperative CT scans of 18 OTSCC patients were reviewed retrospectively by a single observer to measure the DOI on axial and coronal sections; these were then compared to the HPE report. Mean DOI was compared between CECT and HPE using repeated measures ANOVA. The strength of correlation of CT-derived tumour depth was determined using the intra-class correlation coefficient (ICC) followed by assessment of accuracy by Bland-Altman plot. In general, the measurement of DOI was smaller on CECT, with a mean difference of 0.743mm on axial CT and 1.106mm on coronal CT. Regarding the correlation between CECT and HPE tumour depths, ICC was 0.956 for axial CT and 0.965 for coronal CT. Bland-Altman analysis showed that DOI from CECT and histopathological depth were in agreement with each other. In conclusion, there was excellent correlation and accurate measurement of DOI from CECT.

Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines.

Imidazolium salts have shown great promise as anticancer materials. A new imidazolium salt (TPP1), with a triphenylphosphonium substituent, has been synthesized and evaluated for in vitro and in vivo cytotoxicity against bladder cancer. TPP1 was determined to have a GI50 ranging from 200 to 250 µM over a period of 1 h and the ability to effectively inhibit bladder cancer. TPP1 induces apoptosis, and it appears to act as a direct mitochondrial toxin. TPP1 was applied intravesically to a bladder cancer mouse model based on the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Cancer selectivity of TPP1 was demonstrated, as BBN-induced tumors exhibited apoptosis but normal adjacent urothelium did not. These results suggest that TPP1 may be a promising intravesical agent for the treatment of bladder cancer.

Microstructural abnormalities found in uncinate fasciculus and superior cerebellar tracts in children with global developmental delay: a feasibility study.

AIM: To evaluate the microstructural abnormalities of the white matter tracts (WMT) using diffusion tensor imaging (DTI) in children with global developmental delay (GDD). MATERIALS AND METHODS: Sixteen children with GDD underwent magnetic resonance imaging (MRI) and cross-sectional DTI. Formal developmental assessment of all GDD patients was performed using the Mullen Scales of Early Learning. An automated processing pipeline for the WMT assessment was implemented. The DTI-derived metrics of the children with GDD were compared to healthy children with normal development (ND). RESULTS: Only two out of the 17 WMT demonstrated significant differences (p<0.05) in DTI parameters between the GDD and ND group. In the uncinate fasciculus (UF), the GDD group had lower mean values for fractional anisotropy (FA; 0.40 versus 0.44), higher values for mean diffusivity (0.96 versus 0.91×10-3 mm2/s) and radial diffusivity (0.75 versus 0.68×10-3 mm2/s) compared to the ND group. In the superior cerebellar peduncle (SCP), mean FA values were lower for the GDD group (0.38 versus 0.40). Normal myelination pattern of DTI parameters was deviated against age for GDD group for UF and SCP. CONCLUSION: The UF and SCP WMT showed microstructural changes suggestive of compromised white matter maturation in children with GDD. The DTI metrics have potential as imaging markers for inadequate white matter maturation in GDD children.

Clinical implications of molecular subtyping in bladder cancer.

PURPOSE OF REVIEW: The purpose of this review is to examine and evaluate similarities and differences in bladder cancer expression subtypes and to understand the clinical implications of the molecular subtyping. RECENT FINDINGS: Four independent classification systems have been described, and there are broad similarities among the subtyping callers. Two major subtypes have been identified, that is, luminal and basal, with underlying subcategories based on various distinct characteristics. Luminal tumors generally bear a better prognosis and increased survival than basal tumors, although there is subtle variation in prognosis among the different subtypes within the luminal and basal classifications. Clinical subtyping is now commercially available, although there are limitations to its generalizability and application. SUMMARY: Expression subtyping is a new method to personalize bladder cancer management. However, there is probably not sufficient evidence to incorporate use into current standards-of-care. Validation cohorts with clinically meaningful outcomes may further establish the clinical relevance of molecular subtyping of bladder cancer. Additionally, genetic alterations in bladder cancer may 'color' the interpretation of individual tumors beyond the expression subtype to truly personalize care for bladder cancer.

Diagnostic Efficacy of Synthesized 2D Digital Breast Tomosynthesis in Multi-ethnic Malaysian Population.

Synthesized 2D images can be reconstructed from tomosynthesis images in breast imaging. This study aims to investigate the diagnostic efficacy of synthesized 2D images (C-View) in comparison to full field digital mammography (FFDM) when used with digital breast tomosynthesis (DBT) in multi-ethnic Malaysian population. FFDM and C-View images (n = 380) were independently evaluated by three readers through Breast Imaging Reporting and Data System (BI-RADS) categorisation, breast density and lesion characterisation. Statistical analysis was done comparing sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of C-View + DBT with FFDM + DBT as standard of reference. Very good interreader agreement in BI-RADS category and density assessment between C-View + DBT and FFDM + DBT, with high sensitivity, specificity, PPV and NPV of C-View + DBT when compared with FFDM + DBT. There was comparable PPV between C-View + DBT and FFDM + DBT, with histopathology as gold standard. High level of interreader agreement in BI-RADS category and density assessment for FFDM + DBT and C-View + DBT. There was good agreement between FFDM + DBT and C-View + DBT in mass characterization, and almost perfect agreement in calcification and asymmetric density. 52.2% lower radiation dose incurred when using C-View + DBT. Hence, synthesized 2D images are comparable to FFDM with reduction in radiation dose within the limits of Malaysian multi-ethnic population.

Myofibroblastoma of the breast.

INTRODUCTION: Myofibroblastoma is a rare benign mesenchymal tumour arising from the stromal elements of the breast tissue. Histopathological variants such as classic, cellular, collagenous / fibrous, lipomatous, infiltrative, myxoid and epithelioid have been identified. Most myofibroblastomas are immunoreactive for CD34, actin, CD10 and desmin, usually express oestrogen receptor (ER), progesterone receptor (PR) and variably express androgen receptor (AR). CASE REPORT: We report a case of myofibroblastoma in an octogenarian male presenting with painless solitary breast lump. Mammography (digital tomosynthesis) and ultrasound showed a well-circumscribed hyperdense mass and hypoechoic, solid, oval mass with peripheral vascularity respectively. Patient underwent wide local excision. DISCUSSION: Diverse characteristics of myofibroblastoma on imaging necessitates histopathological analysis for an accurate diagnosis. Myofibroblastoma are often confused with fibroadenomas due to the benign imaging characteristics and with malignant neoplasia due to their wide morphological spectrum. Surgical excision is considered curative.

Neuroimaging in refractory epilepsy. Current practice and evolving trends.

Identification of the epileptogenic zone is of paramount importance in refractory epilepsy as the success of surgical treatment depends on complete resection of the epileptogenic zone. Imaging plays an important role in the locating and defining anatomic epileptogenic abnormalities in patients with medically refractory epilepsy. The aim of this article is to present an overview of the current MRI sequences used in epilepsy imaging with special emphasis of lesion seen in our practices. Optimisation of epilepsy imaging protocols are addressed and current trends in functional MRI sequences including MR spectroscopy, diffusion tensor imaging and fusion MR with PET and SPECT are discussed.

Glaucoma severity affects diffusion tensor imaging (DTI) parameters of the optic nerve and optic radiation.

OBJECTIVES: To evaluate whether MR diffusion tensor imaging (DTI) of the optic nerve and optic radiation in glaucoma patients provides parameters to discriminate between mild and severe glaucoma and to determine whether DTI derived indices correlate with retinal nerve fibre layer (RNFL) thickness. METHODS: 3-Tesla DTI was performed on 90 subjects (30 normal, 30 mild glaucoma and 30 severe glaucoma subjects) and the FA and MD of the optic nerve and optic radiation were measured. The categorisation into mild and severe glaucoma was done using the Hodapp-Parrish-Anderson (HPA) classification. RNFL thickness was also assessed on all subjects using OCT. Receiver operating characteristic (ROC) analysis and Spearman's correlation coefficient was carried out. RESULTS: FA and MD values in the optic nerve and optic radiation decreased and increased respectively as the disease progressed. FA at the optic nerve had the highest sensitivity (87%) and specificity (80%). FA values displayed the strongest correlation with RNFL thickness in the optic nerve (r=0.684, p ≤ 0.001) while MD at the optic radiation showed the weakest correlation with RNFL thickness (r=-0.360, p ≤ 0.001). CONCLUSIONS: The high sensitivity and specificity of DTI-derived FA values in the optic nerve and the strong correlation between DTI-FA and RNFL thickness suggest that these parameters could serve as indicators of disease severity.

Differentiation between benign and malignant breast lesions using quantitative diffusion-weighted sequence on 3 T MRI.

AIM: To investigate the capability and diagnostic accuracy of diffusion-weighted imaging (DWI) in differentiating benign from malignant breast lesions using 3 T magnetic resonance imaging (MRI). MATERIALS AND METHODS: Women with suspicious or indeterminate breast lesions detected at MRI, mammogram and/or ultrasound were recruited for dynamic contrast-enhanced (DCE)-MRI and DWI prior to their biopsy. Image fusion of DCE-MRI with apparent diffusion coefficient (ADC) map was utilized to select the region of interest (ROI) for ADC calculation in the area that showed the most avid enhancement. DWI was performed using two sets of b-values at 500 and 1000 s/mm(2), respectively. RESULTS: Fifty women were recruited and the final analysis comprised 44 breast lesions, 31 of which were malignant and 13 were benign. Significant results were obtained between ADC values of benign and malignant lesions (p < 0.001). The cut-off ADC values for benign and malignant lesions were 1.21 × 10(-3) mm(2)/s for b = 500 s/mm(2) and 1.22 × 10(-3) mm(2)/s for b = 1000 s/mm(2), respectively. The sensitivity of DCE-MRI alone was 100% with a specificity of 66.7%. When DCE-MRI was combined with b = 1000 s/mm(2), the specificity rose to 100%, while only mildly affecting sensitivity (90.6%). No significant correlation was found between ADC values and prognostic factors, such as lymph node metastasis, tumour size, oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status, and tumour grades. CONCLUSION: The present study provides consistent evidence to support DWI as a diagnostic tool for breast lesion characterization. A combination of DCE-MRI with DWI is suggested to improve the sensitivity and specificity of lesion characterization.

Improved diagnostic accuracy in differentiating malignant and benign lesions using single-voxel proton MRS of the breast at 3 T MRI.

AIM: To investigate the diagnostic accuracy of single-voxel proton magnetic resonance spectroscopy (SV (1)H MRS) by quantifying total choline-containing compounds (tCho) in differentiating malignant from benign lesions, and subsequently, to analyse the relationship of tCho levels in malignant breast lesions with their histopathological subtypes. MATERIALS AND METHODS: A prospective study of SV 1H MRS was performed following dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in 61 women using a 3 T MR system. All lesions (n = 57) were analysed for characteristics of morphology, contrast-enhancement kinetics, and tCho peak heights at SV (1)H MRS that were two-times above baseline. Subsequently, the tCho in selected lesions (n = 32) was quantified by calculating the area under the curve, and a tCho concentration equal to or greater than the cut-off value was considered to represent malignancy. The relationship between tCho in invasive ductal carcinomas (IDCs) and their Bloom & Richardson grading of malignancy was assessed. RESULTS: Fifty-two patients (57 lesions; 42 malignant and 15 benign) were analysed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of predicting malignancy were 100, 73.3, 91.3, and 100%, respectively, using DCE-MRI and 95.2, 93.3, 97.6, and 87.5%, respectively, using SV (1)H MRS. The tCho cut-off for receiver operating characteristic (ROC) curve was 0.33 mmol/l. The relationship between tCho levels in malignant breast lesions with their histopathological subtypes was not statistically significant (p = 0.3). CONCLUSION: Good correlation between tCho peaks and malignancy, enables SV (1)H MRS to be used as a clinically applicable, simple, yet non-invasive tool for improved specificity and diagnostic accuracy in detecting breast cancer.

Quantification of diffusion tensor imaging in normal white matter maturation of early childhood using an automated processing pipeline.

OBJECTIVES: The degree and status of white matter myelination can be sensitively monitored using diffusion tensor imaging (DTI). This study looks at the measurement of fractional anistropy (FA) and mean diffusivity (MD) using an automated ROI with an existing DTI atlas. METHODS: Anatomical MRI and structural DTI were performed cross-sectionally on 26 normal children (newborn to 48 months old), using 1.5-T MRI. The automated processing pipeline was implemented to convert diffusion-weighted images into the NIfTI format. DTI-TK software was used to register the processed images to the ICBM DTI-81 atlas, while AFNI software was used for automated atlas-based volumes of interest (VOIs) and statistical value extraction. RESULTS: DTI exhibited consistent grey-white matter contrast. Triphasic temporal variation of the FA and MD values was noted, with FA increasing and MD decreasing rapidly early in the first 12 months. The second phase lasted 12-24 months during which the rate of FA and MD changes was reduced. After 24 months, the FA and MD values plateaued. CONCLUSION: DTI is a superior technique to conventional MR imaging in depicting WM maturation. The use of the automated processing pipeline provides a reliable environment for quantitative analysis of high-throughput DTI data. KEY POINTS: Diffusion tensor imaging outperforms conventional MRI in depicting white matter maturation. • DTI will become an important clinical tool for diagnosing paediatric neurological diseases. • DTI appears especially helpful for developmental abnormalities, tumours and white matter disease. • An automated processing pipeline assists quantitative analysis of high throughput DTI data.

Ptosis due to cavernous sinus syndrome as a rare presentation of advanced breast metastasis in a patient with delayed diagnosis.

Complications of breast cancer metastasis may be the first manifestation of the disease. We report a rare case of left eye ptosis secondary to cavernous sinus syndrome in a 34-year-old lady due to refusal of proper medical treatment for metastatic breast cancer. The delay in seeking medical treatment was attributed to her use of Traditional Chinese Medicine (TCM).

Cotton-ball granuloma mimicking axillary lymphadenopathy in a breast cancer patient.

Foreign body granuloma is a reaction to either a biodegradable substance or inert material. In a breast cancer patient who had undergone an excision or mastectomy with axillary clearance, a foreign body granuloma in the axilla may be misinterpreted as an axillary lymph node. We report our experience with a case of cotton-ball granuloma of the axilla in a breast cancer patient, which mimics a lymph node radiologically from the CT scan, mammogram and ultrasonography. Following biopsy and excision, the mass was diagnosed histologically as a foreign body granuloma.

The past, present and future of imaging in multiple sclerosis.

Despite technological advances in imaging, multiple sclerosis (MS) remains a clinical diagnosis that is supported, but not replaced, by laboratory or imaging findings. However, imaging is essential in the current diagnostic criteria of MS, for prediction of the likelihood of MS for patients with clinically isolated syndromes, correlation with lesion pathology and assessment of treatment outcome. This article gives an overview of imaging in MS with particular emphasis on the role of MRI in various diagnostic imaging criteria. Novel imaging for MS using 3 Tesla field strengths, magnetization transfer imaging, diffusion tensor imaging, magnetic resonance spectroscopy and cell-specific contrast will be reviewed.

Epidermal inclusion cyst of the breast: a rare benign entity.

Epidermal inclusion cyst (EIC) arising from the breast is an uncommon benign condition. We report two cases of enlarging EIC of the breast in two women in their forties. The diagnosis of this condition may not be straightforward with imaging alone if an EIC presents as an enlarging lump in the breast and mimics a benign breast lesion, most commonly a fibroadenoma or malignant lesion with benign imaging features. Excision is usually recommended for a definite histopathological diagnosis and for the prevention of potential risks of malignant transformation. Asymptomatic stable lesions do not require treatment; biopsy is unnecessary, and follow-up imaging suffices if typical sonographic and clinical findings are found.