WO2025188805A1 - Blood based rapid diagnostic system for brain hemorrhage detection and associated methods - Google Patents

Abstract

A blood-based diagnostic system for intercranial hemorrhage (ICH) detection includes a sample processing module for processing a blood sample collected from a patient suspected of suffering from ICH, an amino acid detection module for detecting presence of a first amino acid and a second amino acid in the blood sample so processed, an analysis module for calculating a ratio of the first amino acid so detected to the second amino acid so detected to produce a calculation result, and a user interface for communicating the calculation result to a user. In embodiments, the blood-based diagnostic system is implemented as a lateral flow assay. An associated method of operating a blood-based diagnostic system for ICH detection is also disclosed.

Description

Blood based rapid diagnostic system for brain hemorrhage detection and associated methods REFERENCE TO RELATED APPLICATIONS [0001] The present application claims the benefit of US Pat. App. No.63/561,183, filed 2024- 03-04 and titled “Blood based rapid diagnostic system for brain hemorrhage detection and prognosis prediction,” which application is incorporated hereby in its entirety by reference. FIELD OF THE INVENTION [0002] The present invention relates to brain hemorrhage detection. In particular, but not by way of limitation, the present invention relates to detection and evaluation of intracerebral acute hemorrhage by an analysis of a blood sample. DESCRIPTION OF RELATED ART [0003] Brain hemorrhages caused by diseases of the blood vessels or traumatic brain injuries occur in more than one million people in the world each year and in more than 30 thousand people in the USA each year. Intracranial hemorrhage (ICH) may present as epidural hemorrhage, subdural hemorrhage, subarachnoid hemorrhage, or intraparenchymal hemorrhage. Intraparenchymal hemorrhage is a particular type of brain hemorrhage involving bleed into the brain tissue or parenchyma and may occur, for example, due to hypertension, arteriovenous malformation, amyloid angiopathy, aneurysm rupture, tumor, coagulopathy, antithrombotic therapy, infection, vasculitis, advanced age, trauma, and history of cerebrovascular disease. [0004] ICH is recognized as the underlying cause of 10 to 15% of all strokes, with approximately 40,000 to 67,000 cases per year in the US alone. The 30-day mortality rate of all stroke sufferers is 35 to 52%, with half of stroke-related deaths occurring within the first two days, and a 10-year survival rate of 24.1%. Only 27% of stroke patients are functionally independent at 90 days, and a mere 20% are expected to have full functional recovery after 6 months. Further, ICH-induced strokes are known to cause the highest disability rate among the stroke survivors, compared to the outcome from ischemic other subtypes of strokes. [0005] In general, ICH has a 40–50% mortality rate within 30 days and, at one year, mortality ranges from 51–65% depending on the location of the hemorrhage. Additionally, it is speculated that ICH may be the underlying cause of many cases of dementia. [0006] While the harmful effects of ICH are well known, it is currently difficult to diagnose ICH until the symptoms have progressed to a traumatic event. In particular, intraparenchymal hemorrhage is difficult to diagnose without expensive or invasive procedures with significant potential for complications. For instance, a neurological exam may be able to detect more acute cases, albeit with low accuracy. A more sophisticated scan, such as a computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, or angiogram may also be used for ICH diagnosis, although such procedures are costly, low resolution, and may not always be readily available on short notice. A more invasive test, such as the analysis of the cerebral spinal fluid obtained via lumbar puncture, may provide a more accurate detection of ICH, albeit at increased likelihood of complications such as severe headache, brain herniation, back pain, subarachnoid hemorrhage, and infection. In other words, all of these existing diagnostic methods have various shortcomings that make them impractical for diagnosis of acute ICH and/or monitoring of the progression of ICH symptoms over time. [0007] Thus, there is a need for an improved system and method for brain hemorrhage detection and, if possible, assessing prognosis. SUMMARY OF THE INVENTION [0008] The following presents a simplified summary relating to one or more aspects and/or embodiments disclosed herein. As such, the following summary should not be considered an extensive overview relating to all contemplated aspects and/or embodiments, nor should the following summary be regarded to identify key or critical elements relating to all contemplated aspects and/or embodiments or to delineate the scope associated with any particular aspect and/or embodiment. Accordingly, the following summary has the sole purpose to present certain concepts relating to one or more aspects and/or embodiments relating to the mechanisms disclosed herein in a simplified form to precede the detailed description presented below. [0009] In an embodiment a blood based rapid diagnostic system for brain hemorrhage detection and prognosis prediction is disclosed. By comparing concentrations of key markers in a blood sample from a patient, the system may be used to determine whether or not the patient has suffered an episode of intracranial hemorrhage, without the need for complex, expensive, and/or invasive diagnostic procedures. [0010] In certain embodiments, the system may be implemented as a lateral flow assay. In embodiments, the system may be configured to detect multiple analytes for comparison. In certain embodiments, each analyte may be expressed with a distinct color such that the assay results may be visually analyzed by the aggregated color of the assay corresponding to the combination of the concentrations of the different analytes. [0011] In embodiments, the system may be used to analyze the progression of the hemorrhagic condition of a patient over time. In certain embodiments, the system may be used to predict the prognosis of the patient. The prognosis prediction may include the analysis of nitric oxide synthase, in certain embodiments, as an indicator of the potential clinical outcomes of a given patient. [0012] In an embodiment, a blood-based diagnostic system for intercranial hemorrhage (ICH) detection includes a sample processing module for processing a blood sample collected from a patient suspected of suffering from ICH, an amino acid detection module for detecting presence of a first amino acid and a second amino acid in the blood sample so processed, an analysis module for calculating a ratio of the first amino acid so detected to the second amino acid so detected to produce a calculation result, and a user interface for communicating the calculation result to a user. [0013] In embodiments, the system further includes a memory including instructions operating at least one of the sample processing module, the amino acid detection module, and the analysis module. The system further includes a controller including a processor configured for executing the instructions stored on the memory, in certain embodiments. [0014] In embodiments, the analysis module is further configured for predicting a prognosis for the patient. [0015] In certain embodiments, the sample processing module, the amino acid detection module, the analysis module, and the user interface are integrated into a lateral flow assay format. [0016] In an embodiment, a method for operating a blood-based diagnostic system for intercranial hemorrhage (ICH) detection includes processing a blood sample collected from a patient suspected of suffering from ICH, detecting presence of a first amino acid in the blood sample so processed, detecting presence of a second amino acid in the blood sample so processed, calculating a ratio of the first amino acid so detected to the second amino acid so detected to produce a calculation result, and assessing whether the calculation result indicates whether the patient is suffering from ICH. In embodiments, the method may be used to process collected and stored clinical samples of blood, plasma, and/or serum from patients with a variety of conditions, not necessarily acute suspected ICH. [0017] In certain embodiments, the method further includes communicating the calculation result so assessed to a user of the blood-based diagnostic system. [0018] In embodiments, the method further includes analyzing the calculation result in view of clinical data stored in the blood-based diagnostic system, and producing a prediction of prognosis for the patient. [0019] In embodiments, the method further includes assessing a progression of condition of the patient by repeating the steps of processing the blood sample, detecting presence of the first and second amino acids in the blood sample, calculating the ratio, and assessing. [0020] These and other features, and characteristics of the present technology, as well as the methods of operation and functions of the related elements of structure and the combination of parts and economies of manufacture, will become more apparent upon consideration of the following description and the appended claims with reference to the accompanying drawings, all of which form a part of this specification, wherein like reference numerals designate corresponding parts in the various figures. It is to be expressly understood, however, that the drawings are for the purpose of illustration and description only and are not intended as a definition of the limits of the invention. As used in the specification and in the claims, the singular form of 'a', 'an', and 'the' include plural referents unless the context clearly dictates otherwise. BRIEF DESCRIPTION OF DRAWINGS [0021] FIG.1 illustrates the metabolism of the amino acid arginine, its conversion to ornithine and the main enzymes involved in this metabolism. [0022] FIG.2 shows an exemplary electropherogram obtained from a healthy individual. [0023] FIG.3 shows an exemplary electropherogram obtained from an individual suffering from ICH, for comparison with the electropherogram of a healthy individual as shown in FIG.2. [0024] FIG.4 shows the measured concentration values of the metabolite ornithine as measured in a Healthy Controls (HC) group and ICH patients. [0025] FIG.5 shows the measured concentration values of the metabolite arginine as measured in a Healthy Controls (HC) group and ICH patients. [0026] FIG.6 shows the measured concentration values of the metabolite citrulline as measured in a Healthy Controls (HC) group and ICH patients. [0027] FIG.7 shows a scatter plot showing the difference values between the concentration of ornithine minus the concentration of arginine in ICH patients and healthy controls. [0028] FIG.8 shows average values of the difference between concentration of ornithine and concentration of arginine in ICH patients with “good” and “bad” outcomes. [0029] FIG.9 shows comparison of measured arginase values for ICH patients and healthy controls. [0030] FIG.10 shows comparison of measured ODC values for ICH patients and healthy controls. [0031] FIG.11 shows comparison of measured nitric oxide synthase values for ICH patients and healthy controls. [0032] FIG.12 shows a comparison of the measured NO synthase values for ICH patients with good and bad outcomes. [0033] FIGS.13 – 15 are illustrations of a multiplexed lateral flow assay, in accordance with embodiments. In particular, FIG.13 shows a multiplexed lateral flow assay in which a combined fluorescence signal from a test line and a control line is observed and analyzed to obtain the test result, in an embodiment. [0034] FIG.14 shows a multiplexed lateral flow assay in which a first fluorescence signal from a test line and a second fluorescence signal from a control line are observed and analyzed to obtain the test result, in an embodiment. [0035] FIG.15 shows an alternative embodiment of the multiplexed lateral flow assay of FIG. 14, in accordance with certain embodiments. [0036] FIG.16 shows a diagram of a diagnostic system, in accordance with embodiments. [0037] FIG.17 shows a process flow diagram of a method of operating a diagnostic system, in accordance with embodiments. [0038] For simplicity and clarity of illustration, the drawing figures illustrate the general manner of construction, and descriptions and details of well-known features and techniques may be omitted to avoid unnecessarily obscuring the embodiments detailed herein. Additionally, elements in the drawing figures are not necessarily drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help improve understanding of the described embodiments. The same reference numerals in different figures denote the same elements. [0039] The word “exemplary” is used herein to mean “serving as an example, instance, or illustration.” Any embodiment described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments. In the following detailed description, references are made to the accompanying drawings that form a part hereof, and in which are shown by way of illustrations or specific examples. These aspects may be combined, other aspects may be utilized, and structural changes may be made without departing from the present disclosure. Example aspects may be practiced as methods, systems, or apparatuses. The following detailed description is therefore not to be taken in a limiting sense, and the scope of the present disclosure is defined by the appended claims and their equivalents. DETAILED DESCRIPTION OF THE INVENTION [0040] As discussed above, the diagnosis of brain hemorrhages requires very specialized and expensive examinations such as MRI and its variants such as brain imaging using diffusion tensor imaging. Such tests cost several thousands of dollars per procedure and are not available in all hospitals, particularly in rural and remote locations. Further, even if such testing systems are available, any delay in obtaining an accurate diagnosis may have negative impacts on the prognosis of an acute brain hemorrhage patient. [0041] Therefore, a diagnostic test to detect the event of a brain hemorrhage in a simple and timely manner would be greatly desirable. [0042] As the basis of such a diagnostic test for Intraparenchymal hemorrhage, it is recognized herein that certain amino acids are useful as indicators of brain hemorrhage. In particular, it is recognized herein that the relationship between the concentrations of the amino acid arginine and the amino acid ornithine in plasma vary greatly between cerebral hemorrhage patients and healthy individuals. Thus, the ratio between the concentrations of arginine and ornithine may be assessed and used as an indicator of ICH. [0043] Further, as described in detail below, such assessment of the concentrations of these key amino acids may be implemented in an inexpensive assay format, which may be efficiently and effectively administer to patients. Thus, the diagnostic test for brain hemorrhage may be repeatedly administered in even a screening capacity as well as to monitor for the progression of the condition, if ICH is suspected. Such screening and monitoring of patients suspected of suffering from brain hemorrhage are impractical using existing methods of ICH diagnostics. [0044] Moreover, by combining the analysis of the concentration of two key amino acids in patient blood with an analysis of an additional blood enzyme, it is recognized herein that an assessment of patient outcomes after ICH treatment may also be predicted. That is, not only can these amino acid analyses be used as a screening and diagnostic tool, it may also be used as a prognosis forecasting tool. Further, the values of the difference between concentrations of ornithine and arginine in ICH patients may be used to predict the clinical outcome of a given ICH patient. That is, the systems described herein may be used to predict the prognosis of ICH patients without requiring invasive, expensive, and/or complex procedures. [0045] Further, as described in further detail hereinafter, the disclosed system may be further combined with an analysis of the nitric oxide synthase (NOS) as a confirmation of the presence or absence of ICH. The concentration of NOS is also recognized herein as having a good correlation with the clinical outcome of the ICH patient. In other words, the analyses implemented by the system described herein may be used to accurately detect the presence or absence of ICH, track the progress of ICH in a patient, as well as predict the clinical prognosis of the patient over time. Such comprehensive detection, tracking, and prognosis prediction for ICH patients has not been previously available, even with the use of procedures involving expensive and complicated diagnostic machinery. [0046] The diagnostic system described herein not only provides a rapid and cost-effective method for detecting intracerebral hemorrhage through the assessment of ornithine and arginine concentration differentials in blood samples but also establishes a foundation for enhanced prognostic evaluation. Upon positive identification of ICH using this method, clinicians may be prompted to conduct additional t targeted testing, particularly measurement of blood levels of inducible Nitric Oxide Synthase (iNOS). As demonstrated in the clinical validation studies, iNOS plasma concentration is significantly elevated in ICH patients compared to healthy controls, and moreover, shows a strong correlation with clinical outcomes—patients with good outcomes exhibited markedly higher iNOS levels than those with poor outcomes (as illustrated in FIG.12 described in detail below). This cascading diagnostic approach enables healthcare providers to not only detect ICH with greater accessibility and efficiency than traditional imaging methods, but also to stratify patients according to likely prognosis, thereby facilitating more personalized treatment strategies and resource allocation. In other words, the amino acid analysis enables an added benefit of an indication of whether further testing, such as the NOS analysis, would help in providing a better understanding of the patient prognosis, based only on a blood-based diagnostic assay. [0047] Recent studies have shown that polyamine levels in plasma samples from ICH patients are elevated after the ICH occurrence (see, for example, Demel, et al., “Polyamine levels are elevated after intracerebral hemorrhage,” Abstract TP162, Stroke, 2024, https://www.ahajournals.org/doi/10.1161/str.55.suppl_1.TP162#d38853782e1 accessed 2024- 02-05). Beyond elevation of polyamines, it is recognized that the concentration of specific amino acids related to the polyamines can be used in a diagnostic manner. [0048] In particular, the precursor of polyamines is the amino acid arginine. Arginine is a conditional essential amino acid which may be synthesized by the cells of the body and the bacterial enteric flora. However, in critical periods of life and in various diseases, the body consumes arginine faster than it can be synthesized such that a deficiency of the amino acid occurs, unless supplemented by the diet [1, 2]. [0049] Arginine has the following structure: a standard amino acid molecule with its amino group and its carboxyl group linked to the alpha carbon. This alpha carbon links to a propane chain, and the propane chain links to a guanidine group. [0050] FIG.1 illustrates the metabolic pathways of the amino acid arginine, including the conversion to ornithine and the main enzymes involved in this metabolism. The following abbreviations are used in the figure: NOS is nitric oxide synthase; OTCL is ornithine transcarbamylase; CPS is carbamoyl phosphate synthase; ASS is argininosuccinate synthase; ASL, argininosuccinate lyase. As shown in FIG.1, the enzyme arginase separates the carbon of the guanidine group along with two nitrogen atoms to form urea, which the kidneys filter and eliminate in the urine, and the remaining molecule is the amino acid ornithine. Ornithine generally enters the mitochondria via an antiporter that exchanges a citrulline molecule for an ornithine molecule, which process initiates ammonia detoxification inside the mitochondria. [0051] Normally, the human body produces approximately seven grams of ammonia daily. Were this amount of ammonia uniformly distributed throughout the water in the body, the concentration would be approximately 10,000 micromolar. As a concentration of merely three hundred micromolar of ammonia in the blood is considered lethal, the body must consistently eliminate ammonia. [0052] Ammonia detoxification in the mitochondria generally involves the conversion by a group of enzymes to turn ammonia into urea, which is much less toxic than ammonia. For example, ammonia reacts with bicarbonate ions in the presence of adenosine triphosphate (ATP) as an energy donor to form carbamoyl phosphate. The enzyme carbamoyl phosphate synthetase catalyzes the reaction such that carbamoyl phosphate reacts with ornithine within the mitochondria and produces citrulline. The enzyme carbamoyl phosphate synthetase catalyzes this reaction and its product, carbamoyl phosphate, reacts with ornithine to produce citrulline inside the mitochondria. Citrulline is transported to the cytoplasm and reacts with aspartic acid to produce arginosuccinate. The enzyme argininosuccinate synthetase catalyzes the reaction, which requires ATP. In the reaction the ATP molecule breaks down into adenosine monophosphate (AMP) and a pyrophosphate group and the energy released promotes the formation of argininosuccinate. The enzyme argininosuccinate lyase decomposes this molecule into a fumaric acid molecule and an endogenous arginine molecule. [0053] Finally, the enzyme arginase breaks down arginine into urea and ornithine. The kidneys filter urea into the urine and ornithine is available to re-enter the mitochondria and repeat the cycle. In this way, the cells convert highly toxic ammonia molecules into a harmless chemical compound, urea. [0054] Another pathway for the metabolism of arginine is the nitric oxide pathway. For instance, the inducible enzyme, nitric oxide synthase (iNOS) transforms each molecule of arginine into a molecule of citrulline and a molecule of nitric oxide. The enzyme ornithine decarboxylase removes the carboxyl group from the ornithine molecule and produces putrescine and the other polyamines. However, there are no direct reports on the status of the urea cycle of patients suffering from ICH. [0055] In a previous study, Von Holst et al. measured 20 amino acids in the cerebral spinal fluid (CSF) of 13 patients suffering subarachnoid hemorrhage due to rupture of aneurism [3]. They found an increase in all the amino acids including arginine, but not ornithine, both in plasma and in the CSF. Similarly, Sokół et al analyzed 33 compounds, including arginine and ornithine, in the CSF of patients affected by aneurism subarachnoid hemorrhage and found a significant increase in both amino acids, although the relative concentration of arginine and ornithine was not analyzed by Sokół [5]. [0056] Previously, the relationship between the amino acids arginine and ornithine in the CSF has been used to predict the outcome of ruptured aneurysm in the space that separates the brain from the meninges (subarachnoid space) [6]. In this earlier study, the analysis was based on the finding of abundant blood in the CSF retrieved by lumbar puncture, and it was found at that time that there was no difference between the arginine-ornithine ratios (AOR) in these aneurysm patients and the healthy controls. However, the authors noted that those patients who developed a complication called cerebral vasospasm syndrome (CVS), which occurs in 40% to 70% of ruptured aneurism patients, had lower AOR than those of healthy controls. Therefore, AOR in the CSF has been proposed as a method of prognostic for CVS or clinical outcome upon ruptured brain aneurism in the subarachnoid space. [0057] However, as discussed above, intraparenchymal brain hemorrhages produce bleeding inside the brain tissue, therefore it is an entirely different nosological entity compared to a ruptured aneurism causing subarachnoid hemorrhage. Generally, intraparenchymal brain hemorrhage cause CVS in less than 1% of the patients [7], cause less severe symptoms, and have much lower mortality than a ruptured subarachnoid aneurism. [0058] In contrast to previous studies of the diagnostic use of amino acid assessments in brain hemorrhage diagnostics, the present disclosure describes the assessment of the different amino acid concentration measured from a blood sample to detect whether or not a patient has suffered an ICH. Further, by considering a third metabolite, the clinical outcome of the particular patient may also be predicted. [0059] Clinical validation of the usefulness of these metabolite assessments has been performed to demonstrate the usefulness of the assessment of the ratio of arginine and ornithine in patient blood samples in the diagnosis of ICH. For example, in a study involving 33 patients diagnosed as suffering ICH and 33 individuals in a healthy controls (HC) group, the ICH patients had significantly more ornithine and less arginine and citrulline in the blood samples than the HC. That is, there were significant differences in these components of the urea cycle described above, suggesting that there is a disorder in the ammonia detoxification process of ICH patients, and the assessment of the relative ratio between arginine and ornithine levels may be used in diagnosing ICH. As a simple test may involve subtracting the arginine concentration value from the ornithine concentration value in a blood sample, wherein a larger difference between the ornithine and arginine concentration values is an indication of the presence of ICH. [0060] In the exemplary clinical study, the arginine and ornithine values were analyzed using a capillary electrophoresis system with laser-induced fluorescence. Sodium tetraborate, sodium dodecyl sulfate, arginine, ornithine, lysine, sodium hydroxide, perchloric acid, sodium carbonate, sodium bicarbonate, isomer I of fluorescein isothiocyanate and citrulline were used as reagents. Water purified using a commercial water purification system was used during the processing of the samples. [0061] The patient plasma samples were stored at – 80℃, which were thawed on ice to prevent activation of plasma enzymes. While the exemplary clinical study were based on plasma samples, it is recognized herein that arginine and ornithine may be detected and measured in, for example, serum and other biological fluids such as urine. That is, with the appropriate sample processing, the same assessment approaches described herein may be performed using a variety of patient samples, such as whole blood, plasma, serum, and urine. [0062] More particularly, aliquots of 150 microliters were taken and mixed with 75 microliters of 10% aqueous perchloric acid solution. After vigorous vortexing, the aliquot solutions were placed on ice for 30 minutes then centrifuged at 13,000 rpm for one hour in a refrigerated centrifuge at 4˚ Celsius, from which one hundred microliters of supernatant was collected. The collected supernatant was neutralized with 20 microliters of 2.5 Molar sodium hydroxide. Then, 100 microliters of 200 millimolar carbonate buffer were added. Finally, they were mixed with 50 microliters of 2.5 millimolar solution of fluorescein isothiocyanate in acetone and allowed to react in the dark for 24 hours. [0063] The capillary electrophoresis equipment includes a platinum iridium electrode that serves as the anode and another electrode of the same material as the cathode. The detector includes a band-pass filter centered at 490 nanometers, a dichroic mirror that reflects radiation below 510 nanometers and refracts radiation above 510 nanometers, a high-pass filter centered at 520 nanometers, a 60X and 80 numerical aperture objective, a 10X eyepiece and a Hamamatsu model H-9306-02 photomultiplier. The high voltage power source was the Spellman model ARM-30, capable of producing a maximum voltage of 30 kilovolts and a maximum current of 300 microamperes [8] [0064] To separate the analytes, a fused silica capillary of 25 microns internal diameter and 325 microns external diameter with a polyamide cover, 80 centimeters in length and with a 1- centimeter-long window was used. A background electrolyte consisting of a mixture of 40 millimolar sodium tetraborate and 60 millimolar sodium dodecyl sulfate was used to analyze the sample by micellar electrokinetic chromatography [9]. After conditioning the capillary with 1 molar sodium hydroxide, water purified with a commercial water purification system, and background electrolyte solution, the sample was injected into the anodic end of the capillary by applying a negative pressure of 10 psi to the cathodic end of the capillary. A voltage of 30 kilovolts was applied for 30 minutes. The raw output data were collected and processed with custom analysis software developed in-house based on wavelets analysis on the MATLAB® software product.[10] [0065] In the enzymes analysis, the plasma samples were centrifuged at 2,000 rpm for 30 minutes. Then a sample of 10 microliters was used for analysis. Three different enzyme-linked immunosorbent assay (ELISA) kits, for human arginase, human ornithine decarboxylase (ODC) and human iNOS, manufactured by AFG Bioscience were used for the assessment of the enzymes. The plates of these kits were read in an INFINITE® 200 PRO plate reader available from Tecan Trading AG. The wavelength was 450 nm, 50 flashes per reading and 12 reading per circular well. [0066] FIGS.2 and 3 show two exemplary electropherograms, illustrating the differences between the different metabolites that may be observed from samples obtained from a healthy individual and a patient with intracerebral hemorrhage. The electropherogram shown in FIG.2 corresponds to a healthy control. As may be seen in the plot, the size of the peak of ornithine is smaller than the peak of arginine in a healthy individual. [0067] The second electropherogram shown in FIG.3 corresponds to a patient who has suffered an intracerebral hemorrhage. In this case, the peak of ornithine is greater than the peak of arginine, which looks merely like a small bump in the tail of the peak of ornithine. The results of the analysis of ornithine, arginine, and citrulline values as collected from blood plasma samples of the ICH patients and HCs are shown in FIGS.4 – 6, which show the average micromolar concentration value in the y-axis, as measured with the capillary electrophoresis system, for the different amino acids and groups of patients. [0068] As may be seen in FIG.3, the concentrations of the three amino acids measured were significantly altered in the plasma of the ICH patients compared to those values in healthy controls. In particular, the concentration of ornithine increased for ICH patients, while the concentrations of arginine and citrulline decreased. Therefore, it is recognized herein that the arithmetic difference obtained by subtracting the ornithine minus arginine levels is significantly greater in the ICH group than in the HC, thus enabling the detection of ICH. [0069] Furthermore, the differences between micromolar concentration of ornithine minus micromolar concentration of arginine in ICH patients and in healthy controls were compared. The results of the comparison are shown in FIG.7. As may be seen in FIG.4, the difference values (i.e., ornithine micromolar value minus the micromolar value) for the ICH patients were significantly higher than the difference values for the HCs. Thus, the difference values between ornithine and arginine may be a clear indicator of the presence of ICH. [0070] Cognitive measurements were conducted < 1 year from enrollment and included multiple batteries including the Telephone Interview for Cognitive Status (TICS) [4]. Patients with good outcome had a score >35 and patients with bad outcome had a score < 28. The differences in the amino acid levels between ICH patients with “good” outcomes (i.e., recovered from ICH) or “bad” outcomes (i.e., passed away after a certain amount of time) were also studied. It was found that the difference (i.e., the difference in the micromolar concentration values between the “good” and “bad” outcome groups) for the ornithine minus arginine values was significantly lower for ICH patients with bad outcomes, compared to the difference values for the ICH patients with good outcomes (see FIG.8). [0071] Another aspect of enzymatic activity, namely arginase and ornithine decarboxylase (ODC) were also assessed using ELISA. In short, the analysis of three critical enzymes of arginine, ornithine and citrulline metabolism in ICH patients and healthy controls showed virtually no difference of arginase or ornithine decarboxylase but a significant increase of inducible Nitric Oxide Synthase (iNOS) in the plasma of ICH patients (see FIGS.9 - 11). Moreover, the plasma concentration of iNOS was significantly lower in the bad outcome patients as compared with the good outcome patients (see FIG.12) [0072] Arginase and ODC values did not differ significantly between the ICH and HC groups. However, the iNOS plasma concentration was almost double in the ICH group than in the HC group (see FIG.6). This difference in the average NO synthase values between the ICH and HC groups was statistically significant. [0073] The arginase, ODC, and NO synthase results suggest an alteration of the urea and the nitric oxide cycles in patients suffering from intracerebral hemorrhage. The increase in plasma ornithine concentration accompanied by a decrease in arginine concentration suggests that either arginase converts substantial amounts of arginine to ornithine or that ornithine is produced from another source. Such an effect may be speculated as the result of the arginase concentration in plasma not being significantly greater in the ICH patients compared to the HCs. [0074] The decrease in arginine seen in the plasma of patients suffering brain hemorrhage appears to indicate that arginine acts as an essential amino acid. It is known that arginine is one of the main stimulators of mechanistic Target of Rapamycin (mTOR) receptors located on the membrane of lysosomes [12], and the endogenous synthesis of arginine cannot cope with the accelerated metabolism of this amino acid in ICH patients. Therefore, the decrease in arginine may cause a decrease in the activity of the receptors and the mTOR system. This effect in turn should decrease protein synthesis and enhance amino acid recycling through increased autophagy. For instance, Wang et al. have found that mTOR receptors are activated during brain hemorrhages such that blockage of mTOR receptors using rapamycin may produce favorable outcomes of for stroke patients [11, 12]. In this sense, a decrease in arginine may promote recovery after a stroke, which may also explain the favorable evolution that occurs in patients with a greater difference between ornithine and arginine, which may indicate less active mTOR receptors in these patients. [0075] The decrease in serum arginine concentration may be due to an increase in the conversion of arginine in nitric oxide, as possibly supported by the significant increase of plasma iNOS found in the ICH patients compared to the HCs. In a rodent model of ICH, Zhao et al. found an increase of messenger RNA and iNOS protein in the affected tissue [13]. Further, Zhu et al. found that the increase of iNOS in brain ischemia stimulates neurogenesis in the hippocampus of mice [14]. These two findings appear to suggest that the significantly higher plasma iNOS expression in ICH patients may be a factor responsible for their good clinical outcome. [0076] In embodiments, these amino acid concentrations may be obtained from a blood sample, without requiring large imaging systems or complicated procedure such as a lumbar puncture. The assessment of the concentration of these amino acids may be performed in a variety of ways, such as using electrophoresis, a lateral flow assay, a microfluidic assay, a strip test, among others. [0077] For example, a lateral flow assay configured for providing an indication of the arginine to ornithine ratio may provide a readily available point-of-care (POC) test suitable for use by medical professionals as well as, potentially, concerned patients themselves. Such a test may provide a rapid, efficient, and economical assessment at the earliest onset of suspected symptoms, particularly for patients with known or family history of microbleeds or ICH. In this way, a patient may be easily screened to determine whether immediate medical attention is required for ICH, even if clinical symptoms are not yet bothersome. In particular, rapid medical attention can increase the chances for a positive medical or clinical outcome for an ICH patient. [0078] In an embodiment, the brain hemorrhage diagnostic strip may be assembled in a plastic cartridge including a first port for receiving the sample to be analyzed, optionally including a carrier liquid, and a second port for receiving a buffer. In an example, a prescribed amount of a blood sample is placed in the first port, and a prescribed amount of a buffer is added to the second port. In certain embodiments, the blood sample may be processed prior to addition to the brain hemorrhage diagnostic strip by commonly used methods such as centrifuging, mixing with a buffer solution or another chemical, filtering, and others. [0079] In embodiments, a multiplexed lateral flow assay includes a first color indicator for ornithine and a second color indicator for arginine, implemented as a brain hemorrhage diagnostic strip on a commonly available lateral flow assay format, examples illustrated in FIGS. 13 – 15. In embodiments, the components of the brain hemorrhage diagnostic strip are assembled on a backing card (e.g., formed of polyvinyl chloride (PVC)) with an adhesive cover, which provides a protective layer over a series of four pads disposed on the backing card. In an embodiment, a first pad (shown as sample pad in the figures) provides absorption of the sample introduced to the assay. For instance, arginine (represented by a white hexagon within a fluid drop shown as “Sample”) and ornithine (represented by a dark circle within the fluid drop) may be present within a given sample. A second pad serves as a conjugate pad, containing a first antibody to trap arginine and form a first conjugate, and a second antibody to trap ornithine to form a second conjugate. The antibodies may be further linked to gold nanoparticles. A third pad may include a nitrocellulose membrane including detection antibodies forming test and control lines for indicating the test result. A fourth pad may serve as a wicking pad for encouraging the wicking of the sample fluid through the nitrocellulose portion of the assay. [0080] In embodiments, the detection of arginine may be associated with fluorescence of a first color (e.g., red), and the detection of ornithine is associated with fluorescence of a second color (e.g., yellow). In such a case, if both arginine and ornithine are present within a given sample, a combined fluorescence of an orange color would be detectable, with the specific shade of orange being associated with different ratios of arginine and ornithine. [0081] In FIGS.13 – 15, arginine (represented by a white hexagon within a fluid drop) and ornithine (represented by a dark circle within the fluid drop) may be present within a given sample. A control line may be impregnated with antibodies (indicated as Y-shaped icons) capable of binding with one arginine and ornithine. For example, as shown in FIG.13, if both arginine and ornithine are present within a given sample, first and second conjugates are formed such that, once the sample is flowed through the assay, only the control line produces a combined fluorescence including both the first and second colors. Upon mixing, the combined fluorescence serves as an indicator of the presence of arginine and/or ornithine as well as the relative proportion of arginine to ornithine so detected. [0082] Further, the presence of both a test line and a control line indicates the presence of at least one of the analytes. The color of the test line (e.g., an orange line produced when both arginine (associated with a red color) and ornithine (associated with a yellow color) are detected) may be compared with a pre-calibrated color scale by eye or by using an imaging system. As clinically validated, a yellow-ish orange test line color indicates the presence of a higher ratio of ornithine over arginine, which is a strong indicator of the presence of a brain hemorrhage. In contrast, a reddish orange test line is an indication that the patient likely does not have a brain hemorrhage. [0083] If only arginine is present or at higher levels as compared to ornithine within the sample, as shown in FIG.14, then only the first conjugate is formed at the conjugate pad while the second antibody associated with ornithine is allowed to flow through the test and control lines. The test line contains antigens that react in the presence of the second antibody, thus emitting a yellow fluorescence associated with ornithine. The control line then reacts to the first conjugate, associated with arginine, and produces a red fluorescence. It is recognized herein that, in blood samples, both arginine and ornithine are generally detectable in varying ratios, such that the ratio of these amino acids can be used as an indicator of specific conditions. [0084] Similarly, if only ornithine is present or at higher levels as compared to Arginine within the sample, as shown in FIG.15, then the first antibody associated with arginine is allowed to flow through the test and conrol lines while only the second conjugate is formed at the conjugate pad. The test line also contains antigens that react in the presence of the first antibody, thus emitting a red fluorescence associated with ornithine. The control line then reacts to the second conjugate, associated with ornithine, and produces a yellow fluorescence. [0085] In an embodiment, if the levels of arginine and ornithine are approximately equal, then both conjugates will form at the conjugate pad and flow through the test and control lines. In this case, the test line will contain a balanced fluorescence emission, with both red and yellow signals appearing with similar intensity. The control line will also react to both conjugates, showing a combined fluorescence pattern. Such a result may suggest that either: [0086] 1. The onset of a brain hemorrhage, where arginine levels are beginning to increase relative to ornithine; or [0087] 2. A recovery phase from a prior hemorrhage, where arginine levels are decreasing and returning to normal. [0088] The described approach of identification and comparison of specific metabolites may be further expanded to diagnosis and monitoring of the progress of other conditions. For example, similar approaches may be taken in the diagnosis of a variety of other afflictions such as, and not limited to, concussions and/or traumatic brain injury, Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS) and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). Other amino acids (i.e., beyond arginine and ornithine) and/or small molecules may be contemplated to evaluate specific conditions by comparing ratios of their concentrations. Similarly, such modifications may require adjustments and/or use of modified sample processing, specific antibodies as well as different wavelengths for fluorescence detection, and such variations are considered to fall within the scope of the present disclosure. [0089] FIG.16 shows a diagram of a diagnostic system, in accordance with embodiments. As shown in FIG.16, a diagnostic system 1600 includes a sample processing module 1610. Sample processing module 1610 may be as complicated as a suite of laboratory equipment, reagents, and diluents for purification and controlled dilution of a sample, or as simple as a sample pad and conjugate pad of a lateral flow assay, such as illustrated in FIGS.13 – 15. Alternatively, sample processing module may be a laboratory technician performing sample processing in accordance with a prescribed protocol suitable for the diagnostic system, such as preparing samples in a laboratory well plate, microscope slide, or other sample carrying apparatus. [0090] Diagnostic system 1600 further includes an amino acid detection module 1620 for cooperating with the sample processing module. Amino acid detection module 1620 is configured for detecting the presence of two or more different amino acids, for example, using printed antibodies on a lateral flow strip, microscope slide, or a well array, performing fluorescence spectroscopy, capturing and analyzing images of the processed sample, chromatography, mass spectrometry, enzymatic assays, etc. Some examples of such methods include: 1) chromatography-based methods such as High-Performance Liquid Chromatography (HPLC), HPLC with Fluorescence Detection (FLD) (using pre-column derivatization with o- phthalaldehyde or other reagents), HPLC with Ultraviolet (UV) Detection (less sensitive but useful for routine analysis), HPLC with Electrochemical Detection (for increased sensitivity), Reversed-Phase HPLC (RP-HPLC) (most commonly used after derivatization), Gas Chromatography (GC), GC with Mass Spectrometry (GC-MS) (requires derivatization to make amino acids volatile), GC with Flame Ionization Detection (GC-FID), Ion-Exchange Chromatography (IEC), IEC with Post-Column Ninhydrin Detection (such as used in clinical laboratories for amino acid profiling), Automated Amino Acid Analyzers (which rely on IEC with colorimetric detection), Ultra-High-Performance Liquid Chromatography (UHPLC), UHPLC with Tandem Mass Spectrometry (UHPLC-MS/MS); 2) mass spectrometry-based methods such as Liquid Chromatography-Mass Spectrometry (LC-MS), LC-MS/MS (Tandem Mass Spectrometry) (gold standard for specificity and sensitivity), LC-High-Resolution Mass Spectrometry (LC-HRMS) (for research applications), and Capillary Electrophoresis-Mass Spectrometry (CE-MS); 3) Capillary electrophoresis-based methods such as CE with Laser-Induced Fluorescence (CE-LIF) and CE with UV Detection; and 4) Spectrophotometric & Enzymatic Methods, such as Enzymatic Assays (Colorimetric or Fluorometric), Ornithine Decarboxylase Assay (for ornithine quantification), Ninhydrin-Based Assay, Fourier Transform Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR) Spectroscopy. Other approaches are contemplated, such as Point- of-Care systems, electrochemical biosensors, enzyme-based sensors using arginase and/or ornithine decarboxylase for amperometric or potentiometric detection, microfluidic devices, Lab-on-a-Chip systems integrated with colorimetric, fluorescence, or electrochemical detection, and gene/protein expression to assess mRNA or protein levels of these enzymes as indicators of pathway regulation. [0091] Further, measuring activity/levels of nitric oxide can also provide indirect measurements of arginine. Nitric oxide levels can be quantified in various ways, including indirect measurements, such as using eNOS (endothelia Nitric Oxide Synthase), Nitrate (NO₃⁻), Nitrate (NO₃⁻). iNOS and NO Metabolites in plasma may also be quantified by iNOS Protein Concentration (e.g., ELISA or Western blot). Nitric Oxide Metabolites (Nitrate/Nitrite) may also be used as the basis of the assessments described herein. That is, since NO is highly reactive and unstable, NO metabolites (nitrate and nitrite, NOx) may be used as surrogate markers as, in healthy adults, plasma nitrate/nitrite levels typically range between 20–50 µM. Additionally, iNOS mRNA Expression in peripheral blood cells) may be used as an indicator as, in healthy individuals, baseline iNOS gene expression is minimal or undetectable while increasing significantly during infection, inflammation, or sepsis. [0092] Diagnostic system 1600 of FIG.16 further includes an analysis module 1630 for performing a diagnostic analysis. In embodiments, analysis module 1630 calculates a ratio of the two or more different amino acids to make a diagnostic indication. In certain embodiments, the analysis module may include analysis of images captured of fluorescence indicators on a lateral flow strip or other analysis equipment or methods [0093] In embodiments, amino acid detection module 1620 and analysis module 1630 may be encased as a detection/analysis unit 1635. For instance, sample processing module may be configured to produce a processed sample in a format suitable for entry into detection/analysis unit 1635. In embodiments, the production of the processed sample may be performed by a laboratory technician, and the processed sample may be provided to detection/analysis unit 1635 configured, for instance, as a benchtop device suitable for use in a point-of-care or laboratory setting. [0094] Diagnostic system 1600 further includes a user interface 1640 for conveying the results of the analysis performed at analysis module 1630. For instance, in a lateral flow assay format, user interface 1640 may be as simple as a visual indication of fluorescence at a control line and a test line, such as shown in FIGS.13 – 15. Alternatively or additionally, user interface 1640 may be an analog or digital indicator, such as a display screen or light emitting diode array, to communicate the analysis results to a user. [0095] Optionally, the operation of amino acid detection module1620, analysis module 1630, and/or user interface 1640 may be controlled by a controller 1650, which includes processors (not shown) configured to execute instructions stored at a memory 1652 for coordinating the operations of diagnostic system 1600. Further, a communication module 1654 may be connected with user interface 1640, controller 1650, and/or memory 1652 for communicating the analysis results and/or transferring the amino acid detection results to the user. In embodiments, communication module 1654 may include wired and/or wireless communication components, such as an input/output interface, wireless communication chip (e.g., cellular, BLUETOOTH®, or equivalent), and the like. [0096] FIG.17 shows a process flow diagram of a method of operating a diagnostic system, in accordance with embodiments. As shown in FIG.17, an assessment process process 1700 begins with a start step 1702 and proceeds to a step 1710 to process a given sample from a patient. For example, process sample step 1710 may include purification and/or dilution of a sample in a mechanical and/or manual manner. In embodiments, process sample step 1710 may be performed in an automated manner, such as on a lateral flow strip or a microfluidics assay platform including the appropriate flow control and biochemical components integrated therein. [0097] Assessment process 1700 then proceeds to a step 1712 to measure the presence of a first amino acid, a step 1714 to measure the presence of a second amino acid, then calculate a ratio of the first and second amino acids in a step 1716. The ratio so calculated is assessed in a step 1718 to determine whether the ratio indicates a particular condition. For example, in the process of detecting ICH, step 1712 involves the detection of a first amino acid (such as arginine) and step 1714 involves the detection of a second amino acid (such as ornithine). In this case, step 1718 includes determining whether the calculated ratio indicates the presence of ICH in the patient from whom the sample had been collected. [0098] Optionally, assessment process 1700 proceeds to a decision 1730 to determine whether enough data has been collected, such as for a given patient. If the answer to decision 1730 is NO, then assessment process 1700 may return to a step 1710 to, if necessary collect and process an additional sample. If sufficient data has been collected, as determined at decision 1730, then assessment process 1700 optionally proceeds to a step 1732 to analyze the collected data in view of clinical data, such as obtained over the course of a patient study or clinical trial. Then, optionally, assessment process 1700 proceeds to a step 1734 to predict the prognosis for the given patient, such as to predict a clinical outcome or to determine whether additional testing is required for proper assessment of the patient condition. Finally, assessment process 1700 is terminated in an end step 1750. [0099] In certain embodiments, assessment process 1700 may be repeated for a particular patient over time, such as to track the progress of a patient condition. For instance, if assessment process 1700 is implemented using a lateral flow assay as illustrated in FIGS.13 – 15, blood samples of a suspected ICH patient may be collected and analyzed over time to determine whether the ratio of the amino acids of interest indicate possible worsening of a brain hemorrhage, without the need for repeating expensing imaging or invasive procedures. Optionally, the collected data and/or results of the assessment process may be transferred to an external device in an additional step (not shown) via a communication module (e.g., communication module 1654 as shown in FIG.16. [0100] While the detailed description above illustrate specific examples of the contemplated embodiments, various modifications may be contemplated and are considered to be a part of the present disclosure. For example, while certain embodiments are described as enabling quantification of arginine and ornithine from plasma, similar measurements and assessments may be performed using serum samples. Thus, the embodiments described herein are also applicable to assessment processes using blood and/or its derivatives, such as serum. Further, other sample fluids, such as urine, may also be used as the basis of the same testing procedure as described herein. Additionally, the present approach is also applicable for diagnosis in veterinary applications, as it is recognized herein the arginine/ornithine ratio is also an indicator of certain conditions such as ICH in animals. [0101] Further, it is recognized herein that arginine and ornithine levels in biological fluids may be indirectly estimated by measuring the activity or concentration of intermediary enzymes. Some specific examples include: 1) arginase (ARG); 2) nitric oxide synthase (NOS); 3) ornithine transcarbamylase (OTC); 4) arginine decarboxylase (ADC); 5) ornithine decarboxylase (ODC); 6) argininosuccinate synthetase (ASS); and 7) argininosuccinate lyase (ASL). Some approaches for indirect quantification of these intermediary enzymes include, for example: 1) enzyme activity assays for measuring enzymatic activity in plasma, urine, tissue lysates, or other samples; 2) metabolite analysis for quantifying downstream metabolites (e.g., urea, polyamines, nitric oxide) as proxies; and 3) gene/protein expression for assessing mRNA or protein levels of those enzymes as indicators of pathway regulation. [0102] As another application of the approaches described herein, Amyloid-Related Imaging Abnormalities (ARIAs) represent a significant clinical concern in Alzheimer’s disease (AD) patients undergoing monoclonal antibody therapy targeting beta-amyloid. These abnormalities, classified as ARIA-E (edema/effusion) and ARIA-H (hemorrhagic events, including microhemorrhages and hemosiderosis), arise due to vascular amyloid clearance and blood-brain barrier disruption, often in patients with underlying cerebral amyloid angiopathy (CAA). The administration of anti-amyloid monoclonal antibodies, such as aducanumab, lecanemab, and donanemab, has been associated with an increased incidence of ARIA, particularly hemorrhagic complications that may be asymptomatic or manifest as cognitive impairment, headaches, dizziness, or even life-threatening intracerebral hemorrhage. [0103] Currently, MRI remains the primary tool for detecting ARIA-H, yet it presents limitations in accessibility, cost, and real-time monitoring, necessitating an alternative approach for the early, non-invasive detection and surveillance of ARIA-related brain hemorrhages. The assessment approaches described herein may be adapted as a blood-based diagnostic technology for the detection, monitoring, and risk assessment of brain hemorrhage associated with ARIA in Alzheimer’s disease patients undergoing monoclonal antibody therapy. [0104] In embodiments, a method for non-invasive detection and quantification of biomarkers associated with cerebral microhemorrhages, vascular amyloid pathology, and blood-brain barrier dysfunction, wherein biomarker detection is based on the ratio of Arginine to Ornithine (Arg:Orn) in blood or plasma samples, serving as a molecular indicator of neurovascular integrity, endothelial dysfunction, and microhemorrhagic activity is contemplated. The method includes, for example, measurement of Arginine and Ornithine concentrations using a rapid, high-sensitivity assay, wherein deviations in the Arg:Orn ratio correlate with cerebrovascular stress, endothelial damage, and amyloid-associated hemorrhagic risk in Alzheimer's disease patients undergoing monoclonal antibody therapy. The method may further include analysis of Arg:Orn ratio in conjunction with secondary hemorrhagic markers, including but not limited to hemoglobin degradation products, fibrinogen fragments, and inflammatory cytokines, to enhance diagnostic specificity for ARIA-H and blood-brain barrier dysfunction. Further, in certain embodiments, the method may include integration of machine learning-driven biomarker profiling, utilizing Arg:Orn ratio dynamics to predict ARIA-related microhemorrhages, enabling real-time, personalized risk assessment and treatment optimization for patients receiving anti-amyloid monoclonal antibodies. [0105] In embodiments, such an approach of ARIA-H assessment method may include the use of a point-of-care diagnostic tool, leveraging Arg:Orn ratio as a quantifiable, blood-based biomarker for early detection and longitudinal monitoring of cerebrovascular integrity, reducing reliance on neuroimaging while providing clinically actionable insights into the safety and efficacy of Alzheimer’s disease therapies. That is, by employing the Arginine:Ornithine ratio as a core biomarker of cerebrovascular pathology, such an approach provides a heretofore unavailable, non-invasive, and cost-effective approach to identifying and monitoring ARIA-H, optimizing patient safety, and guiding precision treatment strategies in Alzheimer’s disease. In embodiments, this approach may help with monitoring for potential brain bleeding from patients taking monoclonal antibodies against Beta Amyloid conditions, such as ARIA-H. [0106] As used herein, the recitation of "at least one of A, B and C" is intended to mean "either A, B, C or any combination of A, B and C." The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present disclosure. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the disclosure. Thus, the present disclosure is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein. [0107] The terms and expressions employed herein are used as terms and expressions of description and not of limitation, and there is no intention, in the use of such terms and expressions, of excluding any equivalents of the features shown and described or portions thereof. Each of the various elements disclosed herein may be achieved in a variety of manners. This disclosure should be understood to encompass each such variation, be it a variation of an embodiment of any apparatus embodiment, a method or process embodiment, or even merely a variation of any element of these. Particularly, it should be understood that the words for each element may be expressed by equivalent apparatus terms or method terms—even if only the function or result is the same. Such equivalent, broader, or even more generic terms should be considered to be encompassed in the description of each element or action. Such terms can be substituted where desired to make explicit the implicitly broad coverage to which this invention is entitled. [0108] As but one example, it should be understood that all action may be expressed as a means for taking that action or as an element which causes that action. Similarly, each physical element disclosed should be understood to encompass a disclosure of the action which that physical element facilitates. Regarding this last aspect, by way of example only, the disclosure of a “protrusion” should be understood to encompass disclosure of the act of “protruding”— whether explicitly discussed or not—and, conversely, were there only disclosure of the act of “protruding”, such a disclosure should be understood to encompass disclosure of a “protrusion”. Such changes and alternative terms are to be understood to be explicitly included in the description. REFERENCES [0109] 1. Tapiero, H., et al., I. Arginine. Biomedicine & Pharmacotherapy, 2002.56(9): p.439- 445. [0110] 2. Morris, C.R., et al., Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine. Nutr Clin Pract, 2017.32(1_suppl): p.30s-47s. [0111] 3. von Holst, H. and L. Hagenfeldt, Increased levels of amino acids in human lumbar and central cerebrospinal fluid after subarachnoid haemorrhage. Acta Neurochir (Wien), 1985.78(1- 2): p.46-56. [0112] 4. Lines, C.R., et al., Telephone screening for amnestic mild cognitive impairment. Neurology, 2003.60(2): p.261-6. [0113] 5. Sokół, B., et al., Amino Acids in Cerebrospinal Fluid of Patients with Aneurysmal Subarachnoid Haemorrhage: An Observational Study. Front Neurol, 2017.8: p.438. [0114] 6. Zimmermann, J., et al., Arginase-1 Released into CSF After Aneurysmal Subarachnoid Hemorrhage Decreases Arginine/Ornithine Ratio: a Novel Prognostic Biomarker. Transl Stroke Res, 2022.13(3): p.382-390. [0115] 7. Kiphuth, I.C., et al., Vasospasm in intracerebral hemorrhage with ventricular involvement: a prospective pilot transcranial Doppler sonography study. Cerebrovasc Dis, 2011. 32(5): p.420-5. [0116] 8. Hernandez, L., et al., Laser-induced fluorescence and fluorescence microscopy for capillary electrophoresis zone detection. Journal of Chromatography A, 1991.559(1): p.183-196. [0117] 9. Terabe, S., Twenty-five years of micellar electrokinetic chromatography. Procedia Chemistry, 2010.2(1): p.2-8. [0118] 10. Ceballos, G.A., J.L. Paredes, and L.F. Hernández, Pattern recognition in capillary electrophoresis data using dynamic programming in the wavelet domain. Electrophoresis, 2008. 29(13): p.2828-40. [0119] 11. Wang, R., et al., L-Arginine Enhances Protein Synthesis by Phosphorylating mTOR (Thr 2446) in a Nitric Oxide-Dependent Manner in C2C12 Cells. Oxidative Medicine and Cellular Longevity, 2018.2018: p.7569127. [0120] 12. Wang, J.-P. and M.-Y. Zhang, Role for Target of Rapamycin (mTOR) Signal Pathway in Regulating Neuronal Injury after Intracerebral Hemorrhage. Cellular Physiology and Biochemistry, 2017.41(1): p.145-153. [0121] 13. Zhao, X., et al., Distinct patterns of intracerebral hemorrhage-induced alterations in NF-kappaB subunit, iNOS, and COX-2 expression. J Neurochem, 2007.101(3): p.652-63. [0122] 14. Zhu, D.Y., et al., Expression of inducible nitric oxide synthase after focal cerebral ischemia stimulates neurogenesis in the adult rodent dentate gyrus. J Neurosci, 2003.23(1): p.

Claims

Claims 1. A blood-based diagnostic system for intercranial hemorrhage (ICH) detection, the system comprising: a sample processing module for processing a blood sample collected from a patient suspected of suffering from ICH; an amino acid detection module for detecting presence of a first amino acid and a second amino acid in the blood sample so processed; an analysis module for calculating a ratio of the first amino acid so detected to the second amino acid so detected to produce a calculation result; and a user interface for communicating the calculation result to a user.

2. The system of claim 1, further comprising: a memory including instructions operating at least one of the sample processing module, the amino acid detection module, and the analysis module; and a controller including a processor configured for executing the instructions stored on the memory.

3. The system of claim 1, wherein the analysis module is further configured for predicting a prognosis for the patient.

4. The system of claim 1, wherein the sample processing module, the amino acid detection module, the analysis module, and the user interface are integrated into a lateral flow assay format.

5. A method for operating a blood-based diagnostic system for intercranial hemorrhage (ICH) detection, the method comprising: processing a blood sample collected from a patient suspected of suffering from ICH; detecting presence of a first amino acid in the blood sample so processed; detecting presence of a second amino acid in the blood sample so processed; calculating a ratio of the first amino acid so detected to the second amino acid so detected to produce a calculation result; and assessing whether the calculation result indicates whether the patient is suffering from ICH.

6. The method of claim 5, further comprising: communicating the calculation result so assessed to a user of the blood-based diagnostic system.

7. The method of claim 5, further comprising: analyzing the calculation result in view of clinical data stored in the blood-based diagnostic system; and producing a prediction of prognosis for the patient.

8. The method of claim 5, further comprising: assessing a progression of condition of the patient by repeating the steps of processing the blood sample, detecting presence of the first and second amino acids in the blood sample, calculating the ratio, and assessing.