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PubMed2002

Advances in computers and image processing with applications in nuclear medicine.

The continuing advances in hardware performance had made many previously computationally unattractive methods feasible, an example being iterative reconstruction in tomography, which is now routine. Dynamic SPECT can also be performed. However the aim of image processing is not just to produce pretty pictures, but to extract good clinical information. The methods also need to incorporate clinical knowledge and be defined using clinical constraints. In general data in nuclear medicine are n-D, often 3-D plus time. Data reduction for example by the extraction of physiological information, is important. Such data are in any case hard to visualise without compression, for example some kind of dimensionality reduction, going from n-D to a 2-D "functional" image. Both linear and non-linear operations can be considered. To extract physiological data, we need to fit models. Two classes of method are important: data driven and hypothesis driven. Examples of data driven methods are principal component analysis and factor analysis, where the model is derived form the data. Hypothesis driven methods are all implicitly or explicitly based on model fitting. A preliminary data driven step followed by an hypothesis driven approach could be called constrained statistical image analysis. Examples are shown as used in nuclear medicine and are being extended to MRI. Another important problem considered is that of multi-modality image registration and fusion. Although many methods exist, all based on the minimisation of an appropriate distance functions between 2 image data sets such as mutual information, additional constraints are required when the images are not so similar. Additional constraints can be imposed by means of cluster analysis of the n-dimensional feature space. In the analysis of such data, tests against reference data sets (atlases) are required, normally requiring warping the data sets in space, for example by the use of optic flow, or some kind of diffusion equation. Real time analysis of data during acquisition can lead to optimisation of acquisition procedures. Incorporation of such image analysis into a decision support system is desirable.

Algorithms↗

PubMed1996

[The rolandic line: a simple baseline for the identification of the central region. An MRI study and functional validation].

INTRODUCTION: The identification of the central region--i.e. the central sulcus, the pre- and post-central gyri, the paracentral lobule--on MRI and angiographic images may be necessary prior to stereotactic procedures such as biopsies or resection of centrally located tumors, depth electrode recordings for presurgical evaluation of drug-resistant epilepsies, or radiosurgery of arteriovenous malformations. Stereotactic methods, such as the Talairach's proportional grid based on the bicommissural system, demonstrated the statistical position of the central sulcus according to the Ac-Pc, Vac and Vpc baselines. However, the course and the spatial position of this sulcus have remarkable individual differences that sometimes make the sulcus difficult to identify on serial sagittal MRI or lateral angiographic images. In order to facilitate this identification, the authors propose a new oblique baseline, the rolandic (R) line. MATERIAL AND METHODS: The stereotactic MRI and angiography of 22 patients were reviewed for this study. Eleven of these patients had stereotactic biopsies for a low-grade tumor located in the central region, while eleven others had multiple intracerebral electrodes implantation and depth EEG recording (SEEG: stereoelectroencephalography) in the presurgical evaluation of drug-resistant partial epilepsy, prior to epileptogenic cortex resection. The Ac-Pc, Vac, Vpc baselines and segments of the central sulcus were drawn from the mid-sagittal and lateral T1-weighted MRI images and reported on an individual graph. Surface and deep margins as well as axis of the central sulcus were also reported along with corpus callosum baselines as defined by Olivier et al.: horizontal plane, anterior and posterior callosal planes. The rolandic line was then traced from the graph:it joined the intersection point between the anterior callosal plane and an orthogonal line passing through the floor of the temporal fossa, and the intersection point between posterior callosal plane and an orthogonal line passing through the top of the hemisphere. The rolandic line was then superimposed on any sagittal MRI image or lateral stereotactic angiographic film. Finally, the spatial position of electrode contracts through which electrical stimulations elicited motor and/or sensory responses, either from central electrode implanted for motor fibers identification prior to stereotactic biopsies or from SEEG electrodes implanted for epileptogenic zone identification and cortical mapping, was reported on the individual graph. Angular and linear measurements were taken from the graph, between the rolandic line, the central sulcus axis, the Ac-Pc and callosal baselines, and the central sulcus limits (top, bottom, anterior and posterior margins). RESULTS: Graph measurements indicated that the rolandic line was significantly closer to the inferior part of the central sulcus than to its superior part (average distance between the line and the inferior point of the sulcus: 1.86 +/- 1.87 mm; average distance between the line and the superior point of the sulcus: 4.5 +/- 2.3 mm; p < 0.001-t test); similarly, the rolandic line was closer to the deep margin of the sulcus rather than to its superficial border (average distance between the line and the most anterior point of the sulcus: 11.43 +/- 3.16 mm; average distance between the line and the most posterior point of the sulcus: 7.95 +/- 4.14 mm; p < 0.01-t test). In 90% of the cases, the rolandic line followed the deep or middle part of the sulcus, with an average angle of 4.18 degrees +/- 2.53 degrees between the line and the sulcus axis. The spatial position of the electrode contacts that elicited motor/or sensory responses to stimulations correlated topographically well in all cases with the position of the motor and sensory fibers defined according to the central sulcus, baselines and reference to stereotactic atlases. (ABSTRACT TRUNCATED)

Adolescent↗

PubMed2000

Usefulness of the C1 transverse process as a reference guide in the dissection of the upper lateral neck.

In this investigation we dissected 3 cadavers with the lateral cervical approach to assess the usefulness of the transverse process of the atlas (TPA) as a reference guide in the upper lateral neck. Our results indicate that all the important structures in this space can be identified systematically. Lateral to the TPA sits the posterior belly of the digastric muscle, the stylohyoid muscle, and the occipital artery. Anterior to the TPA, the styloid process can be exposed. The internal jugular vein and cranial nerves X, XI, and XII sit between the styloid process and the TPA. Superior to the TPA, tracing the carotid sheath upward, the carotid canal and jugular foramen can be reached. Anteroinferior to the jugular foramen, the hypoglossal nerve emerges from the cranial cavity through the hypoglossal canal. Posterior to the TPA, the suboccipital triangle can be recognized. Within the triangle, the vertebral artery and its accompanying venous complex can be identified.

Cervical Atlas↗

PubMed2000

A stereological approach to human cortical architecture: identification and delineation of cortical areas.

Stereology offers a variety of procedures to analyze quantitatively the regional and laminar organization in cytoarchitectonically defined areas of the human cerebral cortex. Conventional anatomical atlases are of little help in localizing specific cortical areas, since most of them are based on a single brain and use highly observer-dependent criteria for the delineation of cortical areas. In consequence, numerous cortical maps exist which greatly differ with respect to number, position, size and extent of cortical areas. We describe a novel algorithm-based procedure for the delineation of cortical areas, which exploits the automated estimation of volume densities of cortical cell bodies. Spatial sampling of the laminar pattern is performed with density profiles, followed by multivariate analysis of the profiles' shape, which locates the cytoarchitectonic borders between neighboring cortical areas at sites where the laminar pattern changes significantly. The borders are then mapped to a human brain atlas system comprising tools for three dimensional reconstruction, visualization and morphometric analysis. A sample of brains with labeled cortical areas is warped into the reference brain of the atlas system in order to generate a population map of the cortical areas, which describes the intersubject variability in spatial conformation of cortical areas. These population maps provide a novel tool for the interpretation of images obtained with functional imaging techniques.

Brain Mapping↗

PubMed2000

An anatomical atlas to support the virtual planning of hip operations.

Two three-dimensional digitized atlases of a female and a male pelvis were generated to support the virtual 3D-planning of hip operations. Beside the anatomical labeling of bone structures the determination of orthopedic measures, like angles, distances or sizes of contact areas, is important for the planning of hip operations. Thus, each atlas consists of labeled reference CT data sets, a set of landmarks as well as definitions of orthopedic measures and methods for their automatic computation. Furthermore, methods for the automatic transfer of anatomical labels from the atlas to an individual data set are presented resulting in three-dimensional models of the patient's bone structures. The anatomical atlases are designed to replace the interactive, time-consuming pre-processing steps for the virtual 3D operation planning.

Anatomy, Artistic↗

PubMed1994

Stereotactic PET atlas of the human brain: aid for visual interpretation of functional brain images.

UNLABELLED: In the routine analysis of functional brain images obtained by PET, subjective visual interpretation is often used for anatomic localization. To enhance the accuracy and consistency of the anatomic interpretation, a PET stereotactic atlas and localization approach was designed for functional brain images. METHODS: The PET atlas was constructed from a high-resolution [18F]fluorodeoxyglucose (FDG) image set of a normal volunteer (a 41-yr-old woman). The image set was reoriented stereotactically, according to the intercommissural (anterior and posterior commissures) line and transformed to the standard stereotactic atlas coordinates. Cerebral structures were annotated on the transaxial planes by using a proportional grid system and surface-rendered images. The stereotactic localization technique was applied to image sets from patients with Alzheimer's disease, and areas of functional alteration were localized visually by referring to the PET atlas. RESULTS: Major brain structures were identified on both transaxial planes and surface-rendered images. In the stereotactic system, anatomic correspondence between the PET atlas and stereotactically reoriented individual image sets of patients with Alzheimer's disease facilitated both indirect and direct localization of the cerebral structures. CONCLUSION: Because rapid stereotactic alignment methods for PET images are now available for routine use, the PET atlas will serve as an aid for visual interpretation of functional brain images in the stereotactic system. Widespread application of stereotactic localization may be used in functional brain images, not only in the research setting, but also in routine clinical situations.

Adult↗

PubMed2024

SIMS: A deep-learning label transfer tool for single-cell RNA sequencing analysis.

Cell atlases serve as vital references for automating cell labeling in new samples, yet existing classification algorithms struggle with accuracy. Here we introduce SIMS (scalable, interpretable machine learning for single cell), a low-code data-efficient pipeline for single-cell RNA classification. We benchmark SIMS against datasets from different tissues and species. We demonstrate SIMS's efficacy in classifying cells in the brain, achieving high accuracy even with small training sets (<3,500 cells) and across different samples. SIMS accurately predicts neuronal subtypes in the developing brain, shedding light on genetic changes during neuronal differentiation and postmitotic fate refinement. Finally, we apply SIMS to single-cell RNA datasets of cortical organoids to predict cell identities and uncover genetic variations between cell lines. SIMS identifies cell-line differences and misannotated cell lineages in human cortical organoids derived from different pluripotent stem cell lines. Altogether, we show that SIMS is a versatile and robust tool for cell-type classification from single-cell datasets.

Single-Cell Analysis↗

PubMed2003

Evaluation of a segmentation procedure to delineate organs for use in construction of a radiation therapy planning atlas.

OBJECTIVES: This paper evaluates a semi-automatic segmentation procedure to enhance utilizing atlas based treatment plans. For this application, it is crucial to provide a collection of 'reference' organs, restorable from the atlas so that they closely match those of the current patient. To enable assembling representative organs, we developed a semi-automatic procedure using an active contour method. METHOD: The 3D organ volume was identified by defining contours on individual slices. The initial organ contours were matched to patient volume data sets and then superimposed on them. These starting contours were then adjusted and refined to rapidly find the organ outline of the given patient. Performance was evaluated by contouring organs of different size, shape complexity, and proximity to surrounding structures. We used representative organs defined on CT volumes obtained from 12 patients and compared the resulting outlines to those drawn by a radiologist. RESULTS: A strong correlation was found between the area measures of the delineated liver (r = 0.992), lung (r = 0.996) and spinal cord (r = 0.81), obtained by both segmentation techniques. A paired Student's t-test showed no statistical difference between the two techniques regarding the liver and spinal cord (p > 0.05). CONCLUSION: This method could be used to form 'standard' organs, which would form part of a whole body atlas (WBA) database for radiation treatment plans as well as to match atlas organs to new patient data.

Anatomy, Artistic↗

PubMed2004

Opacification of hydrophilic MemoryLens U940A intraocular lenses: analysis of 2 explanted lenses.

PURPOSE: To determine the rate of opacification of hydrophilic MemoryLens U940A intraocular lenses (IOLs) (Mentor Ophthalmics, Inc.) in the given cohort and perform a histopathological and spectrophotometer analysis of 2 explanted opacified IOLs. SETTING: Ophthalmology Department, Faculty Hospital, Nitra, Slovakia. METHOD: This retrospective study comprised 182 patients (205 eyes) who had implantation of a MemoryLens U940A IOL from June 1997 to June 2000. The patients were examined using a slitlamp to detect the presence of IOL opacification. In 4 cases, the lenses were explanted because of significant opacification and patient-reported problems; 2 lenses were provided for further analysis. One unused reference MemoryLens U940A IOL was also evaluated. All IOL were stained with von Kossa to determine the presence of calcium in the opacification. To confirm the components presence of an ultraviolet (UV) absorber, the IOLs were examined with an Avatar 330 Fourier transfer infrared (IR) spectroscope and a UV visible spectrophotometer (Philips). The IR spectrums for the IOL were identified using an IR spectrum atlas. The opacified IOLs, reference IOL, and the IOL packaging were further examined to determine the presence of silicone. RESULTS: Various amounts of opacification were found on the MemoryLens U940A IOL in 30 eyes (30 patients) (14.63%). Two explanted IOLs were positive for von Kossa staining, proving the presence of calcium deposits; the reference lens staining was negative. Spectrophotometry showed that the reference IOL and opacified IOLs were of the same polymer. The presence of the UV absorber on the benzophenone base was seen in the reference lens but not the opacified IOLs. In contrast, an increased concentration of low-molecular-weight components generated during the degradation of the polymer was present in the opacified lenses. The white cover pf the IOL is of polydimethyl siloxane, a silicone rubber. However, no silicone rubber was present in any examined lens, perhaps because the IOLs were in contact with alcohol during the histopathologic examination. CONCLUSIONS: The results indicate opacification of the hydrophilic MemoryLens U940A was caused by premature consumption of the UV absorber in the polymer component of the IOLs optic, with a subsequent degradation of the polymer. Whether silicone from the white cover led to the IOL opacification, as reported with other types of hydrophilic IOLs, could not be confirmed.

Aged↗

PubMedDate not supplied

Hospital charges for a community inpatient palliative care program.

Defining financial parameters of palliative care (PC) is important for providing sustainable programming. In our study, we evaluated hospital length of stay (LOS) and charges for the first 164 inpatient PC consultations performed by the Advanced Illness Assistance (AIA) team at Blount Memorial Hospital (BMH). These AIA patients had a median LOS of 11 days (range, 3-114 days), mean total charges per patient of 65,795 dollars, and mean daily charges of 3,809 dollars. Higher mean daily charges (p = 2.74 E-08, chi-square) were associated with patients who received consultation because of nonphysical symptom reasons. Patients were followed in PC consultation (AIA follow-up days) for a median of five days (range, 1-48), and had mean daily charges of 3,117 dollars. These mean daily charges were 414 dollars less than the charges for the five days prior to PC consultation (pre-AIA days) (p = 0.04, t-test). There was a significant decrease in laboratory and imaging charges during AIA follow-up (p = 0.04, t-test). The study included a reference group of patients whose information was obtained retrospectively from the BMH Atlas (MediQual, Marlborough, MA) database. These reference group patients were hospitalized at BMH during the same time, but they were not seen by the AIA team. The reference group was matched by Diagnosis Related Group (DRG), Admission Severity Grade (ASG), and disposition to the AIA patients. The Atlas patients had a shorter median LOS of six days (range, 1-105 days), and significantly greater mean daily charges of 4,105 dollars (p = 0.006, t-test) compared with AIA patients. Mean daily charges decreased for Atlas patients, as their day of discharge approached (p < 0.001). Estimates of potential charge savings were calculated in two ways: 1) by evaluating the effect of decreasing the LOS of Atlas patients with long LOS (more than seven days) to the level of AIA patients with long LOS, and 2) by comparing the actual mean patient charges during AIA follow-up with using the pre-AIA mean daily charges during the AIA follow-up period and correcting for the effect of decreasing charges that occurred as discharge approached. The estimated savings achieved by decreasing long LOS were more than 100,000 dollars per year, and estimated savings achieved using AIA follow-up charges were more than 1,801,930 dollars per year.

Adult↗

PubMed1977

Radiographs.

Physicians performing radiology for children should utilize modern equipment, expose children to the least amount of radiation possible, and avoid unnecessary examinations. Those interpreting radiographs must be familiar with the wide range of normal variations of the skeleton and/or be prepared to refer to texts and atlases dealing with these. Careful examination of soft tissues greatly increases the accuracy of diagnostic radiology in the search for trauma and infection.

Bone Diseases↗

PubMed2001

New strategies for embedding, orientation and sectioning of small brain specimens enable direct correlation to MR-images, brain atlases, or use of unbiased stereology.

We present a newly developed brain slicing machine and technique for tissue embedding, which enable orientation of fresh or fixed brain tissue from small laboratory animals, in any given position, and subsequent tissue sectioning into slabs with an optional thickness between 0.5 and 20 mm. The oriented tissue slabs may be analysed directly, or processed further on a cryostat or vibratome, into thin stainable histological sections, and aligned to MR-images or brain atlases, depending on the reference used for the initial orientation. Additionally, we describe a new embedding medium (HistOmer) which is an alginate cold polymer ready for instant use after mixing with water. HistOmer allows accurate positioning of the tissue during embedding, and at the same time supports and protects the embedded tissue during sectioning. HistOmer is, therefore, described comprehensively and compared with other commonly used embedding media. This novel slicing technique may also, as illustrated, be used to perform isotropic random orientation of the embedded tissue, before sectioning into tissue slabs of the same thickness. The technique thereby fulfills the requirements for optimal tissue sampling and preparation needed for an unbiased stereologic analysis.

Alginates↗

PubMed2002

MRI-directed subthalamic nucleus surgery for Parkinson's disease.

The subthalamic nucleus (STN) is now regarded as the optimal surgical target for the treatment of medically refractory idiopathic Parkinson's disease. In our center, a predominantly MRI-directed method has been developed for targeting the STN. The STN is localized on T2-weighted images from a 1.5-T MRI scanner. Long acquisition, high-resolution images are acquired in both the axial and coronal planes under strict stereotactic conditions with the patient under general anesthesia. The boundary of STN is co-registered in both planes to give optimal 3-dimensional target definition. Stereotactic coordinates of the dorsolateral STN are recorded and the trajectory is planned down the axis of the nucleus in the coronal plane. Initially, per-operative macrostimulation was used for adjustment at the target prior to unilateral subthalamotomy in 26 patients. Five patients were lost to follow-up. Assessments of the lesions in post-operative images confirmed successful localisation of the lesions within the dorsolateral STN in all of the remaining 21 cases. In a subsequent series of 19 patients treated by deep brain stimulation (DBS), unilateral in 1 patient and bilateral in 18, the STN was targeted using the same MRI-directed method, guide tubes and radio-opaque stylettes were implanted, and target verification was entirely MRI-based. Following implantation of the guide tubes and stylettes, assessments of the per-operative MRI images for the 37 STN targetings confirmed a mean target error, between the stylette and the desired target in the axial plane, of 0.3 mm mediolaterally (SD = 0.4) and 0.4 mm anteroposteriorly (SD = 0.4), with median errors of 0.5 mm. This study demonstrates that MRI-directed targeting of the STN through guide tubes is accurate, and allows direct verification and corrections as necessary. Cumulative frequencies predict that the majority of DBS electrodes placed in this manner will be within 0.5 mm of the planned target. Because physiological methods are not required, the whole procedure can be performed under general anesthesia. We feel that planning with reference to a standard atlas is unreliable and not significantly helped by the addition of microelectrode recording, the accuracy of which in the axial plane is dependent upon the distance between the recording trajectories, which is typically 2 mm.

Electric Stimulation Therapy↗

PubMed2026

ERGA-BGE reference genome of Eunicella cavolini, an IUCN Near Threatened Gorgonian of the Mediterranean Sea.

The Eunicella cavolini reference genome provides an important resource to study the adaptation of this species to different environments and anthropic pressures. This species is impacted by human activities, including climate change, and this reference genome will be useful to study the genomic evolution of this species. The entirety of the genome sequence was assembled into 17 contiguous chromosomal pseudomolecules. This chromosome-level assembly encompasses 0.49 Gb, composed of 159 contigs and 46 scaffolds, with contig and scaffold N50 values of 7.7 Mb and 51.1 Mb, respectively.

Biodiversity Genomics Europe↗

PubMed2026

ERGA-BGE reference genome of the Eurasian Woodcock ( Scolopax rusticola), a game bird species with isolated populations of conservation interest.

The reference genome of the Eurasian Woodcock ( Scolopax rusticola) is an important resource to investigate population structure across the wide breeding range of this iconic game species and the conservation status of specific management units, such as the isolated Macaronesian populations. The genome sequence was assembled into 45 contiguous chromosomal pseudomolecules and 2 sex chromosomes (W and Z). This chromosome-level assembly encompasses 1.2 Gb, composed of 1,613 contigs and 935 scaffolds, with contig and scaffold N50 values of 5.9 Mb and 34.2 Mb, respectively.

Aves↗

PubMed2026

ERGA-BGE chromosome-level genome assembly of the giant stream lacewing  Osmylus fulvicephalus (Scopoli, 1763).

The giant stream lacewing, Osmylus fulvicephalus (Scopoli, 1763), is a widespread European species belonging to the insect order Neuroptera. Its cryptic larvae are predators found at the banks of streams and smaller rivers where they use their piercing, lance-shaped stylets to inject venom into their arthropod prey. Here, we present the reference genome of the giant stream lacewing as a crucial resource for uncovering the genetic basis of venom evolution in Neuroptera. The chromosome-level genome encompasses 674.7 Mb and is composed of 60 contigs and 24 scaffolds where 99.2% of the assembly is distributed among the 6 contiguous chromosomal pseudomolecules and two sex chromosomes (X and Y). Contig and scaffold N50 have a value of 51.5 Mb and 116.2 Mb, respectively. This reference genome is the first genomic resource from the family of lance lacewings, providing valuable data for clarifying the phylogenetic placement of the family Osmylidae within Neuroptera.

Biodiversity Genomics Europe↗

PubMed2026

ERGA-BGE reference genome of the Mediterranean monk seal ( Monachus monachus), an IUCN Vulnerable species.

The Mediterranean monk seal, Monachus monachus, is the only pinniped that lives in the Mediterranean Sea and one of the rarest marine mammals in the world. The species was recently classified as "vulnerable" by the IUCN, considering an improvement in its overall status. However, the species' populations have undergone severe bottlenecks due to systematic persecution by humans over the past centuries. Today, the global population of M. monachus is estimated to be no more than 1,000 individuals. The Mediterranean monk seal is mainly using marine caves as resting and pupping sites. It is an opportunistic apex predator and as a result its role is considered important for maintaining the structure and function of marine ecosystems. Nowadays, the species is threatened mainly by the destruction of its habitat (due to coastal development, mass tourism, and pollution) and by the depletion of its prey due to overfishing. The Mediterranean monk seal is an emblematic species; its ecological importance and its vulnerable status render its protection and effective management necessary. The entirety of the genome sequence of a female specimen was assembled into 16 contiguous chromosomal pseudomolecules, one sex chromosome (X), and one mitochondrial genome. This chromosome-level assembly encompasses 2.4 Gb, composed of 316 contigs and 275 scaffolds, with contig and scaffold N50 values of 90.9 Mb and 157 Mb, respectively.

Biodiversity Genomics Europe↗

PubMed1975

An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions.

One hundred ninety-six whole human breasts were examined by a subgross sampling technique with histologic confirmation. The method permitted the enumeration and identification of essentially all the focal dysplastic, metaplastic, hyperplastic, anaplastic, and neoplastic lesions. Of the 196, 119 were suitable for complete quantitative morphologic analysis of the focal lesions by type. They consisted of 67 breasts obtained by autopsy, 29 cancerous breasts obtained by mastectomy, and 23 contralateral to those with cancer. All lesions, photographed subgrossly, were subsequently confirmed and correlated histologically. Morphologic evidence supported the hypothesis that most lesions traditionally grouped as mammary dysplasia or fibrocystic disease, including apocrine cysts, sclerosing adenosis, fibroadenomas, various forms of lobules (sclerotic, dilated, hypersecretory, hyperplastic, atypical, or anaplastic), ductal carcinoma in situ (DCIS), and lobular carcinoma in situ (LCIS), arose in terminal ductal-lobular units (TDLU) or in the lobules themselves. A probable exception was papilloma of ducts larger than terminal ones. Isolated foci of DCIS within the TDLU were seen in 40% of cancerous breasts, which indicated that the disease often was multifocal. Of the contralateral breasts, the 60% with clinical cancer contained such lesions, and data were in accord with the clinically known fact that women with previous breast cancer have a high rate of the disease in the remaining one. An atypical lobule (AL) of type A (ALA) had the following characteristics: a) It was more common in cancerous breasts or in those contralateral to cancer than in breasts not so identified; b) it had lobular morphology and was a terminal structure on the mammary tree; c) it tended to persist after the menopause, whereas normal lobules usually atrophied; d) it variable degrees of anaplasia forming an arbitrary continuum from normal lobules to ductal carcinoma in situ; and e) as ALA progressed to DCIS, the unfolded lobule resembled a duct which gave the false impression that DCIS was a ductal lesion. The morphologic evidence supported that hypothesis that the lesions herein called AL were derived from TDLU and were precancerous.

Adenocarcinoma, Scirrhous↗